摘要：
Food contaminates, such as insecticide, may influence the toxicity of nanoparticles (NPs) to intestine. The present study investigated the combined toxicity of TiO(2) NPs and fipronil to male mouse intestine. Juvenile mice (8weeks) were orally exposed to 5.74 mg/kg TiO(2) NPs, 2.5mg/kg fipronil, or both, once a day, for 5days. We found that both TiO(2) NPs and fipronil induced some pathological changes in intestines, accompanying with defective autophagy, but these effects were not obviously enhanced after TiO(2) NP and fipronil co-exposure. Fipronil promoted Ti accumulation but induced minimal impact on other trace elements in TiO(2) NP-exposed intestines. Metabolomics data revealed that the exposure altered metabolite profiles in mouse intestines, and two KEGG pathways, namely, ascorbate and aldarate metabolism (mmu00053) and glutathione metabolism (mmu00480), were only statistically significantly changed after TiO(2) NP and fipronil co-exposure. Five metabolites, including 2-deoxy-D-erythro-pentofuranose 5-phosphate, 5alpha-cholestanol, beta-D-glucopyranuronic acid, elaidic acid, and isopentadecanoic acid, and maltotriose, were more significantly up-regulated after the co-exposure, whereas trisaccharide and xylonolactone were only significantly down-regulated by the co-exposure. We concluded that fipronil had minimal impact to enhance the toxicity of TiO(2) NPs to mouse intestines but altered metabolite profiles.
通讯机构：
[Zhang, Z ] J;Jiangsu Univ, Sch Environm & Safety Engn, Zhenjiang 212013, Peoples R China.
摘要：
The DNA-mediated growth strategy of bimetallic nanozymes is considered as an effective approach to regulate their peroxidase activity via tuning the morphology and nanostructure. Albeit important, its biosensing application in rational methods' design and performance improvement is limited due to the deficiency of a systematic understanding of the interactions between DNA and nanomaterials used. Herein, four homo-oligonucleotides as capping ligands were employed to functionalize the bimetallic nanozymes, where Pt nanoparticles (PtNPs) were in situ synthesized onto DNA-bound Au nanorods (AuNRs), and the effects of DNA with different lengths on the state of bimetallic nanozymes were investigated in detail. It was found that the aggregation of AuNRs obviously depended on the variety and number of DNA oligonucleotides with the absorbance ratio at 810 and 525 nm (A810/A525), ranking as follows: AuNRs/A10/PtNPs > AuNRs/G10/PtNPs > AuNRs/C10/PtNPs ≫ AuNRs/T10/PtNPs, which is consistent with the value of K(m) for TMB, indicating that the dispersal/aggregation of the AuNRs is closely related to the deposition and growth of PtNPs, thereby significantly influencing their peroxidase activity. According to our discoveries, a novel colorimetric array platform was fabricated using the above four types of DNA-encoded Pt-Au bimetallic nanozymes as sensing elements for sensitively discriminating the five biological thiols (l-cys, GSH, Hcy, DTT, and Cys-Gly) and identifying the normal cells/tumor cells, respectively. Our work provides a new insight into DNA-programmed bimetallic nanozyme regulation and broadens its sensing applications.
摘要：
Microcystin-LR (MC-LR), the most prevalent and diverse cyanotoxin produced by harmful cyanobacterial blooms, has been linked to gastrointestinal toxicity. Therefore, we conducted a case-control study across four regions in China to investigate this relationship. Inflammatory bowel disease (IBD) cases (219) were matched with healthy controls (438) based on age and gender and conditional logistic regression models and Restricted cubic splines were used to evaluate the association between MC-LR exposure and IBD risk. We used quantitative real-time polymerase chain reaction to measure the expression levels of inflammatory factors. The levels of protein expression in the colorectum were determined using Western blotting (WB). Compared to the lowest quartile of serum MC-LR levels, the adjusted odds ratios and 95% confidence intervals (CI) for the highest quartiles of serum MC-LR levels were 5.51 (2.70, 11.21). The RCS was shown the association between serum MC-LR levels and IBD risk was nonlinear ( P nonlinear < 0.001). In the animal experiments, MC-LR resulted in colorectal injury via the PI3K/AKT signaling pathway. Our study provides the evidence that serum MC-LR exposure is significantly associated with the risk of IBD in China. Animal study results indicate that MC-LR probably causes IBD via the PI3K/AKT signaling pathway.
摘要：
Chlamydia pneumoniae (C. pneumoniae) is a specialized intracellular parasitic pathogen capable of causing pneumonia, sinusitis, bronchitis, and other respiratory diseases, which pose significant public health challenges. Therefore, rapid, accurate, and sensitive diagnosis is crucial for the prevention and treatment of respiratory diseases caused by C. pneumoniae. In this study, we combined enzymatic recombination amplification (ERA) with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 12a system (CRISPR/Cas12a) to develop a dual detection platform termed the Cpn-ERA-CRISPR/Cas12a dual system. This system integrates both the ERA-CRISPR/Cas12a fluorescence system and the ERA-CRISPR/Cas12a lateral flow system. Detection results can be measured using a fluorescence detector or observed with the naked eye on lateral flow strips. The fluorescence system and the lateral flow system detect C. pneumoniae in 30 minutes and 15 minutes, respectively. This dual system exhibits no cross-reactivity with the other seven pathogens, demonstrating high specificity, and achieves a sensitivity of 10(0) copies/µL. Additionally, the Cpn-ERA-CRISPR/Cas12a dual system was employed to analyze 39 clinical samples, comprising 19 positive and 20 negative samples. The detection rate for positive samples was 100%, with no positive results in the negative samples, indicating a high level of concordance with qPCR results. In summary, the Cpn-ERA-CRISPR/Cas12a dual system represents a novel tool for diagnosing C. pneumoniae and holds promising application potential in grassroots community hospitals.
通讯机构：
[Li, L; Chen, SH; Zhen, DS ] U;Univ South China, Coll Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;Hunan Univ, State Key Lab Chemo Biosensing & Chem Engn, Changsha 410082, Peoples R China.
关键词：
Upconversion nanoparticles;Fluorescence resonance energy transfer;Uranyl;Deoxyribozyme;Hybrid chain reaction
摘要：
Anupconversion fluorescence sensing platform was developedwith upconversion nanoparticles (UCNPs) as energy donors and gold nanoparticles (AuNPs) as energy acceptors, based on the FRET principle. They were used for quantitativedetection ofuranyl ions (UO(2)(2+)) by amplifying the signal of the hybrid chain reaction (HCR). When UO(2)(2+) are introduced, the FRET between AuNPs and UCNPs can be modulated through a HCR in the presence of high concentrations of sodium chloride. This platform providesexceptional sensitivity, with a detection limit as low as 68pM for UO(2)(2+) recognition. We have successfully validated the reliability of this method by analyzing authentic water samples, achieving satisfactory recoveries (89.00%-112.50%) that are comparable to those of ICP-MS. These results indicate that the developed sensing platform has the capability to identify trace UO(2)(2+) in complex environmentalsamples.
摘要：
Atherosclerotic disease is a chronic disease that predominantly affects the elderly and is the most common cause of cardiovascular death worldwide. Atherosclerosis is closely related to processes such as abnormal lipid transport and metabolism, impaired endothelial function, inflammation, and oxidative stress. Coenzyme Q10 (CoQ10) is a key component of complex Ⅰ in the electron transport chain and an important endogenous antioxidant that may play a role in decelerating the progression of atherosclerosis. Here, the different forms of CoQ10 presence in the electron transport chain are reviewed, as well as its physiological role in regulating processes such as oxidative stress, inflammatory response, lipid metabolism and cellular autophagy. It was also found that CoQ10 plays beneficial effects in atherosclerosis by mitigating lipid transportation, endothelial inflammation, metabolic abnormalities, and thrombotic processes from the perspectives of molecular mechanisms, animal experiments, and clinical evidence. Besides, the combined use of CoQ10 with other drugs has better synergistic therapeutic effects. It seems reasonable to suggest that CoQ10 could be used in the treatment of atherosclerotic cardiovascular diseases while more basic and clinical studies are needed.
摘要：
Oral exposure to nanoparticles (NPs) may affect intestinal microbiota, and this effect may be further changed by co-contaminates. In the present study, we investigated the combined effects of TiO(2) NPs and fipronil (FPN) on microbiota in mouse intestines. Mice were intragastric exposed to 5.74mg/kg TiO(2) NPs, 2.5mg/kg FPN, or both of them, once a day, for 30 days. The results showed that individual exposure to TiO(2) NPs or FPN decreased body weight and induced pathological changes in intestines. The exposure was also associated with increased cleaved caspase-3 protein, oxidative stress and decreased tight junction protein expression. Furthermore, the levels of diamine oxidase (DAO), lipopolysaccharide (LPS) and inflammatory cytokines in serum were also elevated, indicating increased intestinal barrier permeability. As expected, both TiO(2) NPs and FPN decreased the diversity and altered the composition of microbiota. However, the observed effects were not further enhanced after the co-exposure to TiO(2) NPs and FPN, except that Romboutsia was only significantly increased after the co-exposure to TiO(2) NPs+FPN. We concluded that oral exposure to TiO(2) NPs and FPN showed minimal synergistic effects on microbiota in mouse intestine.
通讯机构：
[Xiao, FB ] U;[Li, JJ] H;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.
关键词：
Dialdehyde carboxymethyl cellulose;Double-network hydrogel;Self-healing;On-demand drug release;Infected wound healing
摘要：
The development of wound dressing materials with both self-healing and antibacterial properties for promoting wound closure is highly desirable in health care. Herein, a smart double-network hydrogel (GS/DPPDH) with promising traits was developed by combining a dynamic Schiff base reaction between dialdehyde carboxymethyl cellulose (DCMC) and poly(ethylene imine) (PEI) with free radical polymerization. Because of its abundant amino groups, the common antibacterial drug gentamycin sulfate (GS) can be loaded into hydrogels by the formation of Schiff base bonds with DCMC. The slightly acidic wound microenvironment caused hydrolysis of the Schiff base bonds, thus releasing the drug GS on-demand. The prepared hydrogel not only showed good self-healing and injectable properties but also displayed excellent blood compatibility and cytocompatibility. The in vitro antibacterial experimental data proved that the GS/DPPDH had high antibacterial ratios of nearly 90% against both gram-positive (S. aureus) and gram-negative (E. coli) bacteria. In addition, in vivo assessment in a mouse model of S. aureus-infected full-thickness skin wounds revealed a wound closure ratio of 83.22 +/- 2.90% after 7 days of healing, which was significantly greater than that in the gauze (59.78 +/- 2.60%) and DPPDH (66.08 +/- 0.21%) groups. Taken together, the results showed that the prepared antibacterial double-network hydrogel with injectable, self-healing, and pH-responsive properties exhibits great potential as a dressing material for infected wound healing.
摘要：
Transition metal doping is an ideal strategy to construct multifunctional and efficient nanozymes for biosensing. In this work, a metal-doped CoMnOx nanozyme was designed and synthesized by hydrothermal reaction and high-temperature calcination. Based on its oxidase activity, an "on-off-on" smartphone sensing platform was established to detect ziram and Cu2+. The obtained flower-shaped CoMnOx could exhibit oxidase-, catalase-, and laccase-like activities. The oxidase activity mechanism of CoMnOx was deeply explored. O-2 molecules adsorbed on the surface of CoMnOx were activated to produce a large amount of O-2(center dot-), and then, O-2(center dot-) could extract acidic hydrogen from TMB to produce blue oxTMB. Meanwhile, TMB was oxidized directly to the blue product oxTMB via the high redox ability of Co species. According to the excellent oxidase-like activity of CoMnOx, a versatile colorimetric detection platform for ziram and Cu2+ was successfully constructed. The linear detection ranges for ziram and Cu2+ were 5 similar to 280 mu M and 80 similar to 360 mu M, and the detection limits were 1.475 mu M and 3.906 mu M, respectively. In addition, a portable smartphone platform for ziram and Cu2+ sensing was established for instant analysis, showing great application promise in the detection of real samples including environmental soil and water.
摘要：
An infrared squaraine dye was utilized to detect Cu2+ in solvents based on H-aggregates of squaraine dye. H-aggregates are a type of aggregation with enhanced photophysical properties compared to monomers. In the presence of a Ca2+ solution, F–Cl offers exceptional H-aggregators that can be transformed into monomers by adding Cu2+. Furthermore, this mode successfully demonstrated fluorescence changes in HeLa cells cultured in vitro after the addition of Ca2+ or Cu2+. A highly specific detection of Cu2+ was achieved using this transformation mode.
通讯机构：
[Wang, FD ; Min, JX ; Fu, GS ] Z;Zhejiang Univ, Key Lab Cardiovasc Intervent & Regenerat Med Zheji, Sir Run Run Shaw Hosp, Dept Cardiol,Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, State Key Lab Expt Hematol,Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Sch Med, Affiliated Hosp 1, Inst Translat Med, Hangzhou, Peoples R China.;Univ South China, Sch Publ Hlth, Sch Basic Med Sci, Affiliated Hosp 1,Hengyang Med Sch, Hengyang, Peoples R China.
摘要：
Pressure overload-induced cardiac hypertrophy is a common cause of heart failure (HF), and emerging evidence suggests that excessive oxidized lipids have a detrimental effect on cardiomyocytes. However, the key regulator of lipid toxicity in cardiomyocytes during this pathological process remains unknown. Here, we used lipidomics profiling and RNA-seq analysis and found that phosphatidylethanolamines (PEs) and Acsl4 expression are significantly increased in mice with transverse aortic constriction (TAC)-induced HF compared to sham-operated mice. In addition, we found that overexpressing Acsl4 in cardiomyocytes exacerbates pressure overload‒induced cardiac dysfunction via ferroptosis. Notably, both pharmacological inhibition and genetic deletion of Acsl4 significantly reduced left ventricular chamber size and improved cardiac function in mice with TAC-induced HF. Moreover, silencing Acsl4 expression in cultured neonatal rat ventricular myocytes was sufficient to inhibit hypertrophic stimulus‒induced cell growth. Mechanistically, we found that Acsl4-dependent ferroptosis activates the pyroptotic signaling pathway, which leads to increased production of the proinflammatory cytokine IL-1β, and neutralizing IL-1β improved cardiac function in Acsl4 transgenic mice following TAC. These results indicate that ACSL4 plays an essential role in the heart during pressure overload‒induced cardiac remodeling via ferroptosis-induced pyroptotic signaling. Together, these findings provide compelling evidence that targeting the ACSL4-ferroptosis-pyroptotic signaling cascade may provide a promising therapeutic strategy for preventing heart failure.
作者机构：
[Li, Yinghui; Tang, Jinzhen; Hu, QH; Li, YH; Hu, Qinghua; Du, Chen; Lyu, Ziquan; Yao, Xiangjie; Fu, Yulin; Shi, Xiaolu; Fang, Shisong; Luo, Guixian] Shenzhen Ctr Dis Control & Prevent, Shenzhen, Guangdong, Peoples R China.;[Peng, Yuejing; Wan, Chengsong] Southern Med Univ, Sch Publ Hlth, BSL 3 Lab Guangdong, Guangdong Prov Key Lab Trop Dis Res, Guangzhou, Guangdong, Peoples R China.;[Lyu, Ziquan] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang, Hunan, Peoples R China.;[Gao, Chenxi] Shanxi Med Univ, Sch Publ Hlth, Taiyuan, Shanxi, Peoples R China.
通讯机构：
[Hu, QH ; Li, YH] S;Shenzhen Ctr Dis Control & Prevent, Shenzhen, Guangdong, Peoples R China.
摘要：
Introduction : The emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineage, BA.2.86, has sparked global public health concerns for its potential heightened transmissibility and immune evasion. Utilizing data from Shenzhen's city-wide wastewater surveillance system, we highlight the presence of the BA.2.86 lineage in Shenzhen. Methods : A mediator probe polymerase chain reaction (PCR) assay was developed to detect the BA.2.86 lineage in wastewater by targeting a specific mutation (Spike: A264D). Between September 19 and December 10, 2023, 781 wastewater samples from 38 wastewater treatment plants (WWTPs) and 9 pump stations in ten districts of Shenzhen were examined. Through multiple short-amplicon sequencing, three positive samples were identified. Results : The BA.2.86 lineage was identified in the wastewater of Futian and Nanshan districts in Shenzhen on December 2, 2023. From December 2 to 10, a total of 21 BA.2.86-positive wastewater samples were found across 6 districts (Futian, Nanshan, Longhua, Baoan, Longgang, and Luohu) in Shenzhen. The weighted average viral load of the BA.2.86 lineage in Shenzhen's wastewater was 43.5 copies/L on December 2, increased to 219.8 copies/L on December 4, and then decreased to approximately 100 copies/L on December 6, 8, and 10. Conclusions : The mediator probe PCR assay, designed for swift detection of low viral concentrations of the BA.2.86 lineage in wastewater samples, shows promise for detecting different SARS-CoV-2 variants. Wastewater surveillance could serve as an early detection system for promptly identifying specific SARS-CoV-2 variants as they emerge.
摘要：
OBJECTIVE: Osteoarticular tuberculosis (OATB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. This study aimed to analyze the clinical epidemiology and drug resistance characteristics of OATB cases in Hunan province which located in South-central China. METHODS: We retrospectively enrolled OATB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital from January 2013 through March 31, 2022. The multiple demographic, clinical variables and drug susceptibility data of the patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods. RESULTS: Of the 269 OATB cases, 197 (73.23%) were males, 206 (76.85%) were farmers; patients' ages ranged from 5 to 85 years, 57 (21.19%) aged at 20-29 years old and 52 (19.33%) aged at 60-69 years old. In terms of the disease, 177 (65.80%) had spinal TB with most occurrence in lumbar vertebrae (26.02%, 70/269), multiple spinal sites (18.96%, 51/269) and thoracic vertebrae (15.24%, 41/269). Outside of the spine, OATB mainly occurred in the lower limb (13.38%, 36/269). In terms of drug resistance, 40 (14.87%) and 72 (26.77%) were resistant to rifampicin (RFP) and isoniazid (INH) respectively; 38 (14.13%) were multi-drug resistant (MDR), and a total of 78 (29.00%) isolates were drug resistant. OATB patients aged 40-49 years old (compared to those aged ≥70 years) and from the west of Hunan province, China (compared to those from the center of Hunan) were at risk for developing RR/MDR (ORs were 5.057 and 4.942, respectively; 95% CIs were 1.009-25.342 and 1.458-16.750, respectively). CONCLUSION: In South-central China, OATB mainly affected males, farmers and those aged 20-29 and 60-69 years old. Spinal TB is prone to occur in the lumbar and multiple spinal sites. The resistance situation of OATB was serious, and people aged 40-49 years old and patients from the west of Hunan were risk factors of RR/MDR. All these findings will help to improve the prevention, diagnosis and treatment strategies of OATB.
作者机构：
[Min, Junxia; Yu, Yingying; Wang, Fudi; Liu, Yutong; Zhou, Jiahui; Yue, Wuyang; Su, Yunxing; Yang, Sisi; Li, Xiaopeng; Min, JX; Sun, Shumin] Zhejiang Univ, Affiliated Hosp 1, Affiliated Hosp 2, Inst Translat Med,Sch Med, Hangzhou 310058, Peoples R China.;[Yu, Yingying; Wang, Fudi; Lin, Zhiting] Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Shah, YM; Shah, Yatrik M.; Das, Nupur K.] Univ Michigan, Div Gastroenterol, Internal Med, Ann Arbor, MI 48109 USA.;[Shah, YM; Shah, Yatrik M.; Das, Nupur K.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.;[Wu, Qian] Zhejiang Univ, Int Inst Med, Sch Med, Yiwu, Zhejiang, Peoples R China.
通讯机构：
[Wang, FD ; Min, JX] Z;[Shah, YM ] U;Zhejiang Univ, Affiliated Hosp 1, Affiliated Hosp 2, Inst Translat Med,Sch Med, Hangzhou 310058, Peoples R China.;Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ Michigan, Div Gastroenterol, Internal Med, Ann Arbor, MI 48109 USA.
关键词：
anemia of inflammation;chemotherapy-induced anemia;FG-4592;HIF;hypoxia;iron-refractory iron deficiency anemia
摘要：
In clinics, hepcidin levels are elevated in various anemia-related conditions, particularly in iron-refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron-refractory anemia, the potential effect of hypoxia and pharmacologically-mimetic drug FG-4592 (Roxadustat) are evaluated, a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor, on mouse models of iron-refractory iron-deficiency anemia (IRIDA), anemia of inflammation and 5-fluorouracil-induced chemotherapy-related anemia. The potent protective effects of both hypoxia and FG-4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG-4592 could stabilize duodenal Hif2 alpha, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin-activated anemias. Moreover, duodenal Hif2 alpha overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2 alpha knockout in the gut significantly delays the recovery from 5-fluorouracil-induced anemia, which can not be rescued by FG-4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia-related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia. In this article, it is demonstrated that targeting the duodenal Hif2 alpha-Fpn axis as a novel strategy to improve refractory hepcidin-activated anemias, including iron-refractory iron-deficiency anemia (IRIDA), inflammatory anemia and chemotherapy-induced anemia, in mice, which provides compelling evidence for further clinical translation.image
作者机构：
[Huang, Guanqin; Liu, Jianjun; Zhou, Li; Yang, Xifei; Wu, Desheng; Huang, Xinfeng; Gao, Chuanyue; Li, Shangming; Nie, Lulin; He, Kaiwu; Zhang, Huan; Yang, XF; Chen, Chongyang] Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Modern Toxicol, Shenzhen Med Key Discipline Hlth Toxicol 2020 2024, Shenzhen 518055, Peoples R China.;[Gao, Chuanyue] Xian Int Med Ctr Hosp, Xian 710100, Peoples R China.;[Yang, Deguang] Jinan Univ, Affiliated Hosp 5, Heyuan Shenhe Peoples Hosp, Dept Cardiol, Heyuan 517000, Peoples R China.;[Nie, Lulin] Jinan Univ, Coll Pharm, Guangzhou 510632, Peoples R China.;[Huang, Zhenlie] Southern Med Univ, Sch Publ Hlth, NMPA Key Lab Safety Evaluat Cosmet, Guangdong Prov Key Lab Trop Dis Res,Dept Toxicol, Guangzhou 510515, Peoples R China.
通讯机构：
[Yang, XF ; Zou, LY ] S;[Zhang, ZH ] U;Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Modern Toxicol, Shenzhen Med Key Discipline Hlth Toxicol 2020 2024, Shenzhen 518055, Peoples R China.;Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp,Clin Med Coll 2,Dept Neurol, Shenzhen, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang 421001, Hunan, Peoples R China.
关键词：
Amyotrophic lateral sclerosis;Copper;Mitophagy;Motor dysfunction;Urolithin A
摘要：
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease pathologically characterized by selective degeneration of motor neurons resulting in a catastrophic loss of motor function. The present study aimed to investigate the effect of copper (Cu) exposure on progression of ALS and explore the therapeutic effect and mechanism of Urolithin A (UA) on ALS. 0.13 PPM copper chloride drinking water was administrated in SOD1(G93A) transgenic mice at 6weeks, UA at a dosage of 50mg/kg/day was given for 6weeks after a 7-week Cu exposure. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl and Immunohistochemistry Staining. Proteomics analysis, Western blotting and ELISA were conducted to detect protein expression. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. Cu-exposure worsened motor function, promoted muscle fibrosis, loss of motor neurons, and astrocyte and microglial activation. It also induced abnormal changes in mitochondria-related biological processes, leading to a significant reduction in ATP levels and an increase in MDA levels. Upregulation of P62 and downregulation of Parkin, PINK1, and LAMP1 were revealed in SOD1(G93A) mice with Cu exposure. Administration of UA activated mitophagy, modulated mitochondria dysfunction, reduced neuroinflammation, and improved gastrocnemius muscle atrophy and motor dysfunction in SOD1(G93A) mice with Cu exposure. Mitophagy plays critical role in ALS exacerbated by Cu exposure. UA administration may be a promising treatment strategy for ALS.
摘要：
This study addresses the energy-intensive nature of conventional wastewater treatment processes and proposes a solution through the development of a green, low-energy, and multifunctional wastewater treatment technology. The research focuses on a multifunctional self-driven photoelectrocatalytic (PEC) system, exploring its four-in-one applications in eliminating organic pollutants, reducing U(VI), generating electrical energy, and disinfecting pathogenic microorganisms. A TiO(2)-decorated carbon felt (CF@TiO(2)) cathode is synthesized to enhance interfacial charge transfer, with TiO(2) coating improving surface binding sites (edge TiO and adsorbed -OH) for UO(2)(2+) adsorption and reduction. The self-driven PEC system, illuminated solely with simulated sunlight, exhibits remarkable efficiency in removing nearly 100% of uranium within 0.5h and simultaneously degrading 99.9% of sulfamethoxazole (SMX) within 1.5h, all while generating a maximum power output density (P(max)) of approximately 1065μW·cm(-2). The system demonstrates significant anti-interference properties across a wide pH range and coexisting ions. Moreover, 49.4% of the fixed uranium on the cathode is reduced into U(IV) species, limiting its migration. The self-driven PEC system also excels in detoxifying various toxic organic compounds, including tetracycline, chlortetracycline, and oxytetracycline, and exhibits exceptional sterilization ability by disinfecting nearly 100% of Escherichia coli within 0.5h. This work presents an energy-saving, sustainable, and easily recyclable wastewater purification system with four-in-one capabilities, relying solely on sunlight for operation.
摘要：
OBJECTIVE: This study aimed to use systematic review and meta-analysis to establish the influence of antifungal therapy on pulmonary Candida colonisation of patients with mechanical ventilation (MV). DESIGN: Systematic review and meta-analysis. DATA SOURCES: An extensive search was undertaken on publications from inception to 25 July 2023, through PubMed, Web of Science, Medline, Embase, China National Knowledge Infrastructure, Wanfang Data and VIP Databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials, cohort studies and case-control studies comparing the efficacy of antifungal treatment in immunocompetent patients with pulmonary Candida colonisation after invasive ventilation. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the data and assessed the quality of studies. Dichotomous outcomes were expressed as ORs with 95% CIs. Continuous outcomes were expressed as standardised mean differences (SMD) with 95% CIs. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes included intensive care unit (ICU), hospital, 28-day, and 90-day mortality. The secondary outcomes included ICU length of stay, MV duration and ventilator-associated pneumonia (VAP). RESULTS: Nine high-quality studies were included. According to the data collected from these nine studies, there is no significant evidence showing a difference between the therapy group treated with antifungal drugs and the control group without antifungal drugs in clinical outcomes, including ICU mortality (OR: 1.37; 95% CI 0.84 to 2.22), hospital mortality (OR: 1.17; 95% CI 0.57 to 2.38), 28-day mortality (OR: 0.71; 95% CI 0.45 to 1.14), 90-day mortality (OR: 0.76; 95% CI 0.35 to 1.63), ICU length of stay (SMD: -0.15; 95% CI -0.88 to 0.59), MV duration (SMD: 0.11; 95% CI -0.88 to 1.10) and VAP (OR: 1.54; 95% CI 0.56 to 4.20). Subgroup analysis of different treatment types indicates that the combined effect size is stable and unaffected by different treatment types including inhalation (OR: 2.32; 95% CI 0.30 to 18.09) and intravenous (OR: 0.65; 95% CI 0.13 to 3.34). CONCLUSION: The application of antifungal treatment did not improve clinical outcomes in patients with MV. We do not suggest initiating antifungal treatment in patients with Candida pulmonary colonisation after invasive ventilation. TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews, CRD42020161138.
