How do food safety technical working groups within a One Health framework work? Experiences from Vietnam and Ethiopia.

BACKGROUND: Persistent challenges of fragmented, food safety management in low- and middle-income countries underscore the need for more robustly coordinated mechanisms. National food safety technical working groups, operating under a One Health framework, offer potential in streamlining coordination efforts to effectively address these challenges. However, more clarity regarding their formation and functioning is important for understanding how to best establish and support such groups. The aim of this study is to systematically document the development process of established groups in Vietnam and Ethiopia. METHODS: We assess the process used to establish and support the technical working groups against six critical success factors for multisectoral collaboration: drive change, define, design, realise, relate, and capture success. To do so, we review meeting minutes, Terms of Reference, and other related publications. RESULTS: The analysis underscores the importance of financial and technical support by development partners in initiating working groups while also highlighting the challenge posed by the absence of legal frameworks to secure government commitment. Embedding the technical working groups within existing government structures - such as One Health platforms - from the outset could help to ensure the active participation and sustainability of such groups. CONCLUSION: Both Vietnam and Ethiopia have established operational and institutionalized technical working groups to bolster national food safety efforts under a One Health framework. The approaches employed in these countries could serve as valuable models for others seeking to establish comparable multisectoral collaborative mechanisms to address emerging health risks.

Label Transfer for Drug Disease Association in Three Meta-Paths.

The identification of potential interactions and relationships between diseases and drugs is significant in public health care and drug discovery. As we all know, experimenting to determine the drug-disease interactions is very expensive in both time and money. However, there are still many drug-disease associations that are still undiscovered and potential. Therefore, the development of computational methods to explore the relationship between drugs and diseases is very important and essential. Many computational methods for predicting drug-disease associations have been developed based on known interactions to learn potential interactions of unknown drug-disease pairs. In this paper, we propose 3 new main groups of meta-paths based on the heterogeneous biological network of drug-protein-disease objects. For each meta-path, we design a machine learning model, then an integrated learning method is formed by these models. We evaluated our approach on 3 standard datasets which are DrugBank, OMIM, and Gottlieb's dataset. Experimental results demonstrate that the proposed method is better than some recent methods such as EMP-SVD, LRSSL, MBiRW, MPG-DDA, SCMFDD,. . . in some measures such as AUC, AUPR, and F1-score.

Transboundary viral diseases of pigs, poultry and ruminants in Southeast Asia: a systematic review.

Livestock is a strategic part of the small-farm economy in Southeast Asia's society, providing food income, clothing, fertilizer, and draught power. However, incidences or outbreaks of transboundary animal diseases (TADs) are due to converging factors such as the natural hazards' aftermath, climate change, deforestation, urban growth, changing production conditions, and market chains. Therefore, this affects productivity and impacts farmers' livelihoods with small holdings. The literature review was carried out to understand the current situation of TADs in Southeast Asia, identifying knowledge gaps to provide actions for disease control and prevention in the region. We have attempted to summarise the scientific literature in English on the prevalence data of TADs in Southeast Asia between 2011 and March 2022. Relatively few studies evaluated the distribution of TAD, where most of the studies focused on diseases that are important for international trade, such as avian influenza (AI), African swine fever (ASF), classical swine fever (CSF), foot-and-mouth disease (FMD) and Newcastle disease (ND). Traditional production systems have received little attention in such studies as they belonged to mainly smallholders. The outbreaks of ASF and lumpy skin disease (LSD) in 2019 resulted in increased research activity between 2019-2022, while the other TADs were ignored in this period. For new emerging TADs diseases such as ASF and LSD, there is only information about the first detection without prevalence information. Therefore, further epidemiological investigations are necessary to reduce the gaps in disease surveillance reporting systems and support the prevention and reduction of further outbreaks.

Study on the temporal and spatial distribution of Culex mosquitoes in Hanoi, Vietnam.

Arboviruses transmitted by mosquitoes, including Japanese encephalitis virus (JEV), present a substantial global health threat. JEV is transmitted by mosquitoes in the genus Culex, which are common in both urban and rural areas in Vietnam. In 2020, we conducted a 1-year survey of Culex mosquito abundance in urban, suburban, and peri-urban areas of Hanoi using CDC-light traps. Mosquitoes were identified to species and sorted into pools based on species, sex, and trap location. The mosquito pools were also investigated by RT-qPCR for detection of JEV. In total, 4829 mosquitoes were collected over a total of 455 trap-nights, across 13 months. Collected mosquitoes included Culex, Aedes, Anopheles, and Mansonia species. Culex mosquitoes, primarily Cx. quinquefasciatus, predominated, especially in peri-urban areas. Most Culex mosquitoes were caught in the early months of the year. The distribution and abundance of mosquitoes exhibited variations across urban, suburban, and peri-urban sites, emphasizing the influence of environmental factors such as degree of urbanization, temperature and humidity on Culex abundance. No JEV was detected in the mosquito pools. This study establishes baseline knowledge of Culex abundance and temporal variation, which is crucial for understanding the potential for JEV transmission in Hanoi.

Dendritic cell-targeted delivery of antigens using extracellular vesicles for anti-cancer immunotherapy.

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large-scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell-derived EVs (RBCEVs) targeting splenic DEC-205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen-reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti-DEC-205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings.

Supernatant of platelet-Klebsiella pneumoniae coculture induces apoptosis-like death in Klebsiella pneumoniae.

Multidrug-resistant Klebsiella pneumoniae strains, especially carbapenem-resistant K. pneumoniae, have become a rapidly emerging crisis worldwide, greatly limiting current therapeutic options and posing new challenges to infection management. Therefore, it is imperative to develop novel and effective biological agents for the treatment of multidrug-resistant K. pneumoniae infections. Platelets play an important role in the development of inflammation and immune responses. The main component responsible for platelet antibacterial activity lies in the supernatant stimulated by gram-positive bacteria. However, little research has been conducted on the interaction of gram-negative bacteria with platelets. Therefore, we aimed to explore the bacteriostatic effect of the supernatant derived from platelet-K. pneumoniae coculture and the mechanism underlying this effect to further assess the potential of platelet-bacterial coculture supernatant. We conducted this study on the gram-negative bacteria K. pneumoniae and CRKP and detected turbidity changes in K. pneumoniae and CRKP cultures when grown with platelet-K. pneumoniae coculture supernatant added to the culture medium. We found that platelet-K. pneumoniae coculture supernatant significantly inhibited the growth of K. pneumoniae and CRKP in vitro. Furthermore, transfusion of platelet-K. pneumoniae coculture supernatant alleviated the symptoms of K. pneumoniae and CRKP infection in a murine model. Additionally, we observed apoptosis-like changes, such as phosphatidylserine exposure, chromosome condensation, DNA fragmentation, and overproduction of reactive oxygen species in K. pneumoniae following treatment with the supernatant. Our study demonstrates that the platelet-K. pneumoniae coculture supernatant can inhibit K. pneumoniae growth by inducing an apoptosis-like death, which is important for the antibacterial strategies development in the future.IMPORTANCEWith the widespread use of antibiotics, bacterial resistance is increasing, and a variety of multi-drug resistant Gram-negative bacteria have emerged, which brings great challenges to the treatment of infections caused by Gram-negative bacteria. Therefore, finding new strategies to inhibit Gram-negative bacteria and even multi-drug- resistant Gram-negative bacteria is crucial for treating infections caused by Gram-negative bacteria, improving the abuse of antibiotics, and maintaining the balance between bacteria and antibiotics. K. pneumoniae is a common clinical pathogen, and drug-resistant CRKP is increasingly difficult to cure, which brings great clinical challenges. In this study, we found that the platelet-K. pneumoniae coculture supernatant can inhibit K. pneumoniae growth by inducing an apoptosis-like death. This finding has inspired the development of future antimicrobial strategies, which are expected to improve the clinical treatment of Gram-negative bacteria and control the development of multidrug-resistant strains.

Emerging zoonotic diseases in Southeast Asia in the period 2011-2022: a systematic literature review.

As COVID-19 has shown, pandemics and outbreaks of emerging infections such as Zika, Nipah, monkeypox and antimicrobial-resistant pathogens, especially emerging zoonotic diseases, continue to occur and may even be increasing in Southeast Asia. In addition, these infections often result from environmental changes and human behaviour. Overall, public health surveillance to identify gaps in the literature and early warning signs are essential in this region. A systematic review investigated the prevalence of emerging zoonotic diseases over 11 years from 2011 to 2022 in Southeast Asia to understand the status of emerging zoonotic diseases, as well as to provide necessary actions for disease control and prevention in the region. During the 2011-2022 period, studies on pigs, poultry, ruminants, companion animals and wildlife in Southeast Asia were reviewed thoroughly to assess the quality of reporting items for inclusion in the systematic review. The review was performed on 26 studies of pigs, 6 studies of poultry, 21 studies of ruminants, 28 studies of companion animals and 25 studies of wildlife in Southeast Asia, which provide a snapshot of the prevalence of the emerging zoonotic disease across the country. The findings from the review showed that emerging zoonotic diseases were prevalent across the region and identified a few zoonotic diseases associated with poultry, mainly stemming from Cambodia and Vietnam, as high priority in Southeast Asia.Clinical relevance: Appropriate prevention and control measures should be taken to mitigate the emerging zoonotic diseases in Southeast Asia.

TGF-ß1 and TGF-ß3, but not TGF-ß2, are upregulated in the ovaries of ovarian hyperstimulation syndrome†.

Ovarian hyperstimulation syndrome (OHSS) is a life-threatening and potentially fatal complication during in vitro fertilization treatment. The levels of transforming growth factor-ß1 (TGF-ß1) are upregulated in human follicular fluid and granulosa-lutein cells (hGL) of OHSS patients and could contribute to the development of OHSS by downregulating steroidogenic acute regulatory protein (StAR) expression. However, whether the same is true for the other two members of the TGF-ß family, TGF-ß2 and -ß3, remains unknown. We showed that all three TGF-ß isoforms were expressed in human follicular fluid. In comparison, TGF-ß1 was expressed at the highest level, followed by TGF-ß2 and TGF-ß3. Compared to non-OHSS patients, follicular fluid levels of TGF-ß1 and TGF-ß3 were significantly upregulated in OHSS patients. The same results were observed in mRNA levels of TGF-ß isoforms in hGL cells and ovaries of OHSS rats. In addition, StAR mRNA levels were upregulated in hGL cells of OHSS patients and the ovaries of OHSS rats. Treatment cells with TGF-ß isoforms downregulated the StAR expression with a comparable effect. Moreover, activations of SMAD3 signaling were required for TGF-ß isoforms-induced downregulation of StAR expression. This study indicates that follicular fluid TGF-ß1 and TGF-ß3 levels could be used as biomarkers and therapeutic targets for the OHSS.

Improving astaxanthin-loaded chitosan/polyvinyl alcohol/graphene oxide nanofiber membranes and their application in periodontitis.

Periodontitis is a chronic inflammatory disease primarily driven by host inflammation and plaque-induced immune responses. Controlling the host inflammatory response and improving the periodontal inflammatory microenvironment are crucial to promoting periodontal tissue regeneration. In this study, the blended nanofiber membranes previously prepared by our research group were improved, and we developed multifunctional chitosan/polyvinyl alcohol/graphene oxide/astaxanthin coaxial nanofiber membranes. Scanning electron microscopy showed that the prepared nanofibers had a smooth surface and a uniform diameter distribution. The mechanical property test results showed that the coaxial nanofiber membranes exhibited higher tensile strength compared to the blended nanofiber membranes, which increased from 4.50 ± 0.32 and 3.70 ± 0.45 MPa to 7.12 ± 0.22 and 5.62 ± 0.79 MPa respectively. Drug release studies indicated that the "shell-core" structure of coaxial nanofibers significantly reduced the initial burst release of astaxanthin (ASTA), with only 13.49 % and 10.71 % release in the first 24 h, and drug release lasted for over a week. Animal experiments confirmed that the coaxial nanofiber membranes loaded with ASTA promoted periodontal bone defect repair while inhibiting periodontal inflammation. In conclusion, the prepared coaxial nanofiber membranes are a promising sustained-release drug system for treating periodontitis.

Investigating charge traps in MoTe2field-effect transistors: SiO2insulator traps and MoTe2bulk traps.

Two-dimensional material-based field-effect transistors are promising for future use in electronic and optoelectronic applications. However, trap states existing in the transistors are known to hinder device performance. They capture/release carriers in the channel and lead to hysteresis in the transfer characteristics. In this work, we fabricated MoTe2field-effect transistors on two different gate dielectrics, SiO2and h-BN, and investigated temperature-dependent charge trapping behavior on the hysteresis in their transfer curves. We observed that devices with SiO2back-gate dielectric are affected by both SiO2insulator traps and MoTe2intrinsic bulk traps, with the latter becoming prominent at temperatures above 310 K. Conversely, devices with h-BN back-gate dielectric, which host a negligible number of insulator traps, primarily exhibit MoTe2bulk traps at high temperatures, enabling us to estimate the trap energy level at 389 meV below the conduction band edge. A similar energy level of 396 meV below the conduction band edge was observed from the emission current transient measurement. From a previous computational study, we expect these trap states to be the tellurium vacancy. Our results suggest that charge traps in MoTe2field-effect transistors can be reduced by careful selection of gate insulators, thus providing guidelines for device fabrication.

Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3.

PURPOSE: Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. PATIENTS AND METHODS: We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. RESULTS: The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. CONCLUSION: Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.

Effect of light-touch intervention and associated factors to microbial contamination at small-scale pig slaughterhouses and traditional pork shops in Vietnam.

Traditional pork value chains dominate the production and distribution of pork in Vietnam; however, the high level of microbiological contamination in pork may increase the risk of food-borne disease for consumers. There is limited evidence about how to feasibly and scalably reduce microbial contamination in pork sold in traditional markets. This study aimed to assess the effectiveness of light-touch interventions for changing worker behaviour in small-scale slaughterhouses and vendors at traditional pork shops, as well as to identify risk factors for pork contamination. The intervention packages consisted of providing hygiene tools and delivering a food safety training which had been designed in a participatory way and covered 10 small-scale slaughterhouses and 29 pork shops. Pig carcasses, retailed pork, contact surfaces, and hands were sampled to measure the total bacterial count (TBC) and Salmonella contamination before, three and six weeks after the intervention, and trainee practices were observed at the same time. Linear and generalized linear mixed effects models were constructed to identify risk factors for TBC and Salmonella contamination at the slaughterhouses and pork shops. The interventions at slaughterhouses and pork shops both showed a slight reduction of TBC contamination in pig carcasses and Salmonella prevalence in retailed pork, while the TBC in retailed pork decreased only marginally. For slaughterhouses, the regression model indicated that smoking or eating during slaughtering (indicating poor hygienic practices) was associated with TBC increasing, while cleaning floors and wearing boots reduced TBC contamination. For pork shops, using rough materials (cardboard or wood) to display pork was the only factor increasing TBC contamination in pork, whereas cleaning knives was associated with lower TBC. Besides, the presence of supporters and wearing aprons reduced the probability of Salmonella contamination in pork. The findings highlight the effectiveness of light-touch interventions in reducing microbial contamination in pig carcasses at small-scale slaughterhouses and pork at traditional shops over the study period.

Polymer-Based Hydrogels Applied in Drug Delivery: An Overview.

Polymer-based hydrogels are hydrophilic polymer networks with crosslinks widely applied for drug delivery applications because of their ability to hold large amounts of water and biological fluids and control drug release based on their unique physicochemical properties and biocompatibility. Current trends in the development of hydrogel drug delivery systems involve the release of drugs in response to specific triggers such as pH, temperature, or enzymes for targeted drug delivery and to reduce the potential for systemic toxicity. In addition, developing injectable hydrogel formulations that are easily used and sustain drug release during this extended time is a growing interest. Another emerging trend in hydrogel drug delivery is the synthesis of nano hydrogels and other functional substances for improving targeted drug loading and release efficacy. Following these development trends, advanced hydrogels possessing mechanically improved properties, controlled release rates, and biocompatibility is developing as a focus of the field. More complex drug delivery systems such as multi-drug delivery and combination therapies will be developed based on these advancements. In addition, polymer-based hydrogels are gaining increasing attention in personalized medicine because of their ability to be tailored to a specific patient, for example, drug release rates, drug combinations, target-specific drug delivery, improvement of disease treatment effectiveness, and healthcare cost reduction. Overall, hydrogel application is advancing rapidly, towards more efficient and effective drug delivery systems in the future.

Antioxidant Activities, Anticancer Activity, Physico-Chemistry Characteristics, and Acute Toxicity of Alginate/Lignin Polymer.

Alginate/lignin is a synthetic polymer rich in biological activity and is of great interest. Alginate is extracted from seaweed and lignin is extracted from corn stalks and leaves. In this paper, antioxidant activities of alginate/lignin were evaluated, such as total antioxidant activity, reducing power activity, DPPH free radical scavenging activity, and α-glucosidase inhibition activity. Anticancer activity was evaluated in three cell lines (Hep G2, MCF-7, and NCI H460) and fibroblast. Physico-chemistry characteristics of alginate/lignin were determined through FTIR, DSC, SEM_EDS, SEM_EDS mapping, XRD, XRF, and 1H-NMR. The acute toxicity of alginate/lignin was studied on Swiss albino mice. The results demonstrated that alginate/lignin possessed antioxidant activity, such as the total antioxidant activity, and reducing power activity, especially the α-glucosidase inhibition activity, and had no free radical scavenging activity. Alginate/lignin was not typical in cancer cell lines. Alginate/lignin existed in a thermally stable and regular spherical shape in the investigated thermal region. Six metals, three non-metals, and nineteen oxides were detected in alginate/lignin. Some specific functional groups of alginate and lignin did not exist in alginate/lignin crystal. Elements, such as C, O, Na, and S were popular in the alginate/lignin structure. LD0 and LD100 of alginate/lignin in mice were 3.91 g/kg and 9.77 g/kg, respectively. Alginate/lignin has potential for applications in pharmaceutical materials, functional foods, and supporting diabetes treatment.

How can climate change and its interaction with other compounding risks be considered in evaluation? Experiences from Vietnam.

While evaluations play a critical role in accounting for and learning from context, it is unclear how evaluations can take account of climate change. Our objective was to explore how climate change and its interaction with other contextual factors influenced One Health food safety programs. To do so, we integrated questions about climate change into a qualitative evaluation study of an ongoing, multi-sectoral program aiming to improve pork safety in Vietnam called SafePORK. We conducted remote interviews with program researchers (n = 7) and program participants (n = 23). Based on our analysis, researchers believed climate change had potential impacts on the program but noted evidence was lacking, while program participants (slaughterhouse workers and retailers) shared how they were experiencing and adapting to the impacts of climate change. Climate change also interacted with other contextual factors to introduce additional complexities. Our study underscored the importance of assessing climate factors in evaluation and building adaptive capacity in programming.

Exploring the Multitarget Activity of Wedelolactone against Alzheimer's Disease: Insights from In Silico Study.

In this study, Wedelolactone's multitarget activity against Alzheimer's disease was examined using density functional theory and molecular docking techniques. At physiological pH, the pK a and molar fractions have been estimated. The most likely relative rate constants of two radical scavenger mechanisms are formal hydrogen transfer in a lipid environment and single-electron transfer in a water solvent. Compared to Trolox (k overall = 8.96 × 104 M-1 s-1), Wedelolactone (k overall = 4.26 × 109 M-1 s-1) is more efficient in scavenging the HOO• radical in an aqueous environment. The chelation capacity of metals was investigated by examining the complexation of the Cu(II) ion at various coordination positions and calculating the complexation kinetic constants. Furthermore, molecular docking simulations showed that the known forms of Wedelolactone at physiological pH effectively inhibited the AChE and BChE enzymes by comparing their activity to that of tacrine (control). Wedelolactone is a promising drug candidate for Alzheimer's disease therapy in light of these findings.

Antimicrobial resistance and molecular characterization of Escherichia coli isolated from bovine mastitis samples in Nghe An province, Vietnam.

Background and Aim: Vietnam's dairy sector is in its early phase of large-scale farming development. Therefore, mastitis in cows is always a concern to farm owners. This study aimed to determine the antimicrobial susceptibility, resistance, and virulence-related genes of Escherichia coli isolated from bovine mastitis in Nghe An province of Vietnam. Materials and Methods: Fifty E. coli strains were isolated from the clinical cases and subjected to this study. All isolates were tested for antimicrobial susceptibility by the disk-diffusion method, as described by the Clinical and Laboratory Standards Institute. Antimicrobial and virulence genes were confirmed by polymerase chain reaction with specific primers. Results: All isolates were resistant to lincomycin and sulfamethoxazole and sensitive to gentamicin, while other antimicrobials showed resistance from 2% to 90%. Multidrug resistance was confirmed in 46% of isolates, and none of them were identified as extended-spectrum beta-lactamase producers. From fifty strains tested for antimicrobial and virulence genes, six isolates harbored tetA, 6 tetB, 13 sul1, 15 sul2, 2 Intimin (eae), 1 iutA, and 3 stx2. Conclusion: Antimicrobial and multidrug resistances are the main virulence factors of E. coli isolated from bovine mastitis in Vietnam. The virulence genes encoding adhesion, siderophore, Shiga-toxin-producing, and antimicrobials resistant were first reported in Vietnam with low prevalence and contributed to the pathogenesis.

TGF-ß1 upregulates secreted protein acidic and rich in cysteine expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a serious complication during in vitro fertilization (IVF) treatment. The upregulation of ovarian transforming growth factor-beta 1 (TGF-ß1) is involved in the development of OHSS. The secreted protein acidic and rich in cysteine (SPARC) is a secreted multifunctional matricellular glycoprotein. Although the regulatory effects of TGF-ß1 on SPARC expression have been reported, whether TGF-ß1 regulates SPARC expression in the human ovary remains unknown. In addition, the role of SPARC in the pathogenesis of OHSS is unclear. METHODS: A steroidogenic human ovarian granulosa-like tumor cell line, KGN, and primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing IVF treatment were used as experimental models. OHSS was induced in rats, and ovaries were collected. Follicular fluid samples were collected from 39 OHSS and 35 non-OHSS patients during oocyte retrieval. The underlying molecular mechanisms mediating the effect of TGF-ß1 on SPARC expression were explored by a series of in vitro experiments. RESULTS: TGF-ß1 upregulated SPARC expression in both KGN and hGL cells. The stimulatory effect of TGF-ß1 on SPARC expression was mediated by SMAD3 but not SMAD2. The transcription factors, Snail and Slug, were induced in response to the TGF-ß1 treatment. However, only Slug was required for the TGF-ß1-induced SPARC expression. Conversely, we found that the knockdown of SPARC decreased Slug expression. Our results also revealed that SPARC was upregulated in the OHSS rat ovaries and in the follicular fluid of OHSS patients. Knockdown of SPARC attenuated the TGF-ß1-stimulated expression of vascular endothelial growth factor (VEGF) and aromatase, two markers of OHSS. Moreover, the knockdown of SPARC reduced TGF-ß1 signaling by downregulating SMAD4 expression. CONCLUSIONS: By illustrating the potential physiological and pathological roles of TGF-ß1 in the regulation of SPARC in hGL cells, our results may serve to improve current strategies used to treat clinical infertility and OHSS. Video Abstract.

Microbial Contamination and Antibiotic Resistance in Marketed Food in Bangladesh: Current Situation and Possible Improvements.

Antimicrobial resistance (AMR) is a public health problem worldwide. Bangladesh, like its neighboring countries, faces many public health challenges, including access to safe food, inadequate food surveillance, as well as increasing AMR. This study investigated bacterial contamination and the AMR profile of pathogens in marketed food in Bangladesh and explored barriers to reducing AMR in the country. We collected 366 tomatoes, 359 chicken and 249 fish samples from 732 vendors in traditional markets in urban, peri-urban and rural areas in Bangladesh, as well as from 121 modern retails in Dhaka capital to analyse Vibrio cholerae and Escherichia coli in fish, Salmonella in chicken, and Salmonella and E. coli in tomatoes. Antibiotic susceptibility against 11 antibiotics was tested using a disc diffusion test and interpreted by an automated zone inhibition reader. In addition, a qualitative study using key informant interviews was conducted to explore antimicrobial use and AMR reduction potential in Bangladesh. We found E. coli in 14.21% of tomatoes and 26.91% of fish samples, while 7.38% of tomatoes and 17.27% of chicken were positive for Salmonella, and 44.98% of fish were positive for Vibrio cholerae. In total 231/319 (72.4%) of all pathogens isolated were multidrug-resistant (MDR) (resistant to three or more antibiotic groups). Qualitative interviews revealed an inadequate surveillance system for antibiotic use and AMR in Bangladesh, especially in the agriculture sector. To be able to fully understand the human health risks from bacterial hazards in the food and the AMR situation in Bangladesh, a nationwide study with a one health approach should be conducted, within all sectors, including AMR testing as well as assessment of the antimicrobial use and its drivers.

Piezocatalytic 2D WS2 Nanosheets for Ultrasound-Triggered and Mitochondria-Targeted Piezodynamic Cancer Therapy Synergized with Energy Metabolism-Targeted Chemotherapy.

Piezoelectric nanomaterials that can generate reactive oxygen species (ROS) by piezoelectric polarization under an external mechanical force have emerged as an effective platform for cancer therapy. In this study, piezoelectric 2D WS2 nanosheets are functionalized with mitochondria-targeting triphenylphosphonium (TPP) for ultrasound (US)-triggered, mitochondria-targeted piezodynamic cancer therapy. In addition, a glycolysis inhibitor (FX11) that can inhibit cellular energy metabolism is loaded into TPP- and poly(ethylene glycol) (PEG)-conjugated WS2 nanosheet (TPEG-WS2 ) to potentiate its therapeutic efficacy. Upon US irradiation, the sono-excited electrons and holes generated in the WS2 are efficiently separated by piezoelectric polarization, which subsequently promotes the production of ROS. FX11-loaded TPEG-WS2 (FX11@TPEG-WS2 ) selectively accumulates in the mitochondria of human breast cancer cells. In addition, FX11@TPEG-WS2 effectively inhibits the production of adenosine triphosphate . Thus, FX11@TPEG-WS2 exhibits outstanding anticancer effects under US irradiation. An in vivo study using tumor-xenograft mice demonstrates that FX11@TPEG-WS2 effectively accumulated in the tumors. Its tumor accumulation is visualized using in vivo computed tomography . Notably, FX11@TPEG-WS2 with US irradiation remarkably suppresses the tumor growth of mice without systemic toxicity. This study demonstrates that the combination of piezodynamic therapy and energy metabolism-targeted chemotherapy using mitochondria-targeting 2D WS2 is a novel strategy for the selective and effective treatment of tumors.