Rapid visual detection of Helicobacter pylori and vacA subtypes by Dual-Target RAA-LFD assay.

BACKGROUND: Helicobacter pylori (H. pylori) infects over 50% of the global population and is a significant risk factor for gastric cancer. The pathogenicity of H. pylori is primarily attributed to virulence factors such as vacA. Timely and accurate identification, along with genotyping of H. pylori virulence genes, are essential for effective clinical management and controlling its prevalence. METHODS: In this study, we developed a dual-target RAA-LFD assay for the rapid, visual detection of H. pylori genes (16s rRNA, ureA, vacA m1/m2), using recombinase aided amplification (RAA) combined with lateral flow dipstick (LFD) methods. Both 16s rRNA and ureA were selected as identification genes to ensure reliable detection accuracy. RESULTS: A RAA-LFD assay was developed to achieve dual-target amplification at a stable 37 °C within 20 min, followed by visualization using the lateral flow dipstick (LFD). The whole process, from amplification to results, took less than 30 min. The 95 % limit of detection (LOD) for 16 s rRNA and ureA, vacA m1, vacA m2 were determined as 3.8 × 10-2 ng/µL, 5.8 × 10-2 ng/µL and 1.4 × 10-2 ng/µL, respectively. No cross-reaction was observed in the detection of common pathogens including Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis, showing the assay's high specificity. In the evaluation of the clinical performance of the RAA-LFD assay. A total of 44 gastric juice samples were analyzed, immunofluorescence staining (IFS) and quantitative polymerase chain reaction (qPCR) were used as reference methods. The RAA-LFD results for the 16s rRNA and ureA genes showed complete agreement with qPCR findings, accurately identifying H. pylori infection as confirmed by IFS in 10 out of the 44 patients. Furthermore, the assay successfully genotyped vacA m1/m2 among the positive samples, showing complete agreement with qPCR results and achieving a kappa (κ) value of 1.00. CONCLUSION: The dual-target RAA-LFD assay developed in this study provides a rapid and reliable method for detecting and genotyping H. pylori within 30 min, minimizing dependency on sophisticated laboratory equipment and specialized personnel. Clinical validation confirms its efficacy as a promising tool for effectively control of its prevalence and aiding in the precise treatment of H. pylori-associated diseases.

Association Between Extreme Heat and Outpatient Visits for Mental Disorders: A Time-Series Analysis in Guangzhou, China.

Previous evidence on heatwaves' impact on mental health outpatient visits is limited, especially uncertainty on how different heatwave definitions affect this relationship. In this time-series study, we assessed the association between heatwaves and outpatient visits for mental disorders in Guangzhou, China. Daily outpatient visits for mental disorders and its specific categories (schizophrenia, mood, and neurotic disorders) were sourced from the Urban Resident-based Basic Medical Insurance (URBMI) and the Urban Employee-based Basic Medical Insurance (UEBMI) claims databases in Guangzhou from 2010 to 2014. The study employed nine heatwave definitions, based on combinations of three daily mean temperature thresholds (90th, 92.5th, and 95th percentiles) and durations (2, 3, and 4 days). Using quasi-Poisson generalized linear models (GLMs), we estimated the risks (at lag 0 day) and cumulative effects (lag 0-10 days) of heatwaves on mental disorder outpatient visits. Age, gender, types of medical insurance were considered as potential effect modifiers. We observed a positive association between heatwaves and increased total outpatient visits for mental disorders, both at lag 0 day and during lag 0-10 days. The impact of heatwave was significant at lag 0 day for schizophrenia, mood and neurotic disorders visits, it remained significant for neurotic and mood disorders visits during lag 0-10 days. Heatwave durations lasting more than 4 days were associated with higher relative risks of mental disorders at lag 0 day. Older adults had relatively higher effect estimations than younger individuals. This research highlights the effects of extreme heat on mental health.

Nanoceria-induced variations in leaf anatomy and cell wall composition drive the increase in mesophyll conductance of salt-stressed cotton leaves.

Nanomaterials as an emerging tool are being used to improve plant's net photosynthetic rate (AN) when suffering salt stress, but the underlying mechanisms remain unclear. To clarify this, a hydroponic experiment was conducted to study the effects of polyacrylic acid coated nanoceria (PNC) on the AN of salt-stressed cotton and related intrinsic mechanisms. Results showed that the PNC-induced AN enhancement of salt-stressed leaves was strongly facilitated by the mesophyll conductance to CO2 (gm). Further analysis showed that the PNC-induced improvement of gm was related to the increased chloroplast surface area exposed to intercellular airspaces, which was attribute to the increased mesophyll surface area exposed to intercellular airspaces and chloroplast number due to the increased K+ content and decreased reactive oxygen species level in salt-stressed leaves. Interestingly, our results also showed that PNC-induced variations in cell wall composition of salt-stressed cotton leaves strongly influenced gm, especially, hemicellulose and pectin. Moreover, the proportion of pectin in cell wall composition played a more important role in determining gm. Our study demonstrated for the first time that nanoceria, through alterations to anatomical traits and cell wall composition, drove gm enhancement, which ultimately increased AN of salt-stressed leaves.

Brightening triplet excitons enable high-performance white-light emission in organic small molecules via integrating n-π*/π-π* transitions.

Luminescent materials that simultaneously embody bright singlet and triplet excitons hold great potential in optoelectronics, signage, and information encryption. However, achieving high-performance white-light emission is severely hampered by their inherent unbalanced contribution of fluorescence and phosphorescence. Herein, we address this challenge by pressure treatment engineering via the hydrogen bonding cooperativity effect to realize the mixture of n-π*/π-π* transitions, where the triplet state emission was boosted from 7% to 40% in isophthalic acid (IPA). A superior white-light emission based on hybrid fluorescence and phosphorescence was harvested in pressure-treated IPA, and the photoluminescence quantum yield was increased to 75% from the initial 19% (blue-light emission). In-situ high-pressure IR spectra, X-ray diffraction, and neutron diffraction reveal continuous strengthening of the hydrogen bonds with the increase of pressure. Furthermore, this enhanced hydrogen bond is retained down to the ambient conditions after pressure treatment, awarding the targeted IPA efficient intersystem crossing for balanced singlet/triplet excitons population and resulting in efficient white-light emission. This work not only proposes a route for brightening triplet states in organic small molecules, but also regulates the ratio of singlet and triplet excitons to construct high-performance white-light emission.

Antimicrobial blue light inactivation of Pseudomonas aeruginosa: Unraveling the multifaceted impact of wavelength, growth stage, and medium composition.

Pseudomonas aeruginosa, a notable pathogen frequently associated with hospital-acquired infections, displays diverse intrinsic and acquired antibiotic resistance mechanisms, posing a significant challenge in infection management. Antimicrobial blue light (aBL) has been demonstrated as a potential alternative for treating P. aeruginosa infections. In this study, we investigated the impact of blue light wavelength, bacterial growth stage, and growth medium composition on the efficacy of aBL. First, we compared the efficacy of light wavelengths 405 nm, 415 nm, and 470 nm in killing three multidrug resistant clinical strains of P. aeruginosa. The findings indicated considerably higher antibacterial efficacy for 405 nm and 415 nm wavelength compared to 470 nm. We then evaluated the impact of the bacterial growth stage on the efficacy of 405 nm light in killing P. aeruginosa using a reference strain PAO1 in exponential, transitional, or stationary phase. We found that bacteria in the exponential phase were the most susceptible to aBL, followed by the transitional phase, while those in the stationary phase exhibited the highest tolerance. Additionally, we quantified the production of reactive oxygen species (ROS) in bacteria using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and flow cytometry, and observed a positive correlation between aBL efficacy and ROS production. Finally, we determined the influence of growth medium on aBL efficacy. PAO1 was cultivated in brain heart infusion (BHI), Luria-Bertani (LB) broth or Casamino acids (CAA) medium, before being irradiated with aBL at 405 nm. The CAA-grown bacteria exhibited the highest sensitivity to aBL, followed by those grown in LB broth, and the BHI-grown bacteria demonstrated the lowest sensitivity. By incorporating FeCl3, MnCl2, ZnCl2, or the iron chelator 2,2'-bipyridine (BIP) into specific media, we discovered that aBL efficacy was affected by the iron levels in culture media.

EBV-associated epithelial cancers cells promote vasculogenic mimicry formation via a secretory cross-talk with the immune microenvironment.

Background: Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated. Methods: IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. In vitro and in vivo evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets. Results: EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers. Conclusions: Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages.

Towards Efficient White-light Emission in Sulfur Dots through Surface Charge Engineering.

Sulfur dots (SDs) have emerged as promising photoluminescence (PL) materials owing to their intrinsic merits such as abundant electronic effects, outstanding biocompatibility and available photocatalytic activity. Typically based on quantum confinement effects, SDs are reported usually confined emission in blue-to-green region. However, it is challenging to achieve their broad emission tunability in the visible region, restricted by inherent band gap of bulk sulfur (ca. 2.79 eV). Herein, we present white-light-emitting SDs achieved by surface charge engineering that hybridizes the surface of SDs with oleylamine. The resulting SDs exhibit broadband emissions (full width at half maximum of 187 nm) with PL quantum yields of up to 12.1% and Commission International de I'Eclairage color coordinates of (0.27, 0.32). Detailed experimental and calculation results reveal that the strong orbital coupling between oleylamine and sulfur on the hybrid surfaces of the SDs causes electron delocalization, leading to the generation of low-energy charge transfer (CT) states. These CT states are highly sensitive to sulfur-oleylamine hybrid structures, which complicate the transition dynamics and promote multi-energy emission, accounting for efficient white-light emission. The demonstration of white-light SDs based on surface charge engineering is an important step towards the development of sulfur-based PL materials.

Effects of modification methods on the structural characteristics and functional properties of dietary fiber from cucumber.

Cucumbers produce by-products such as cucumber pomace during processing and most of them are discarded without being utilized. To effectively utilize the waste, cucumber pomace is used to extract both insoluble and soluble dietary fibers (DFs) using compound enzyme method (ME), High pressure processing assisted ME (HPP-ME), and dynamic high-pressure microfluidization-assisted ME (DHPM-ME). The results showed that DHPM-ME improved the extraction rate of soluble DFs most effectively, increasing it from 1.74 % to 4.08 %. The modified DFs exhibited enhanced hydration properties and functional properties after HPP-ME- and DHPM-ME-mediated auxiliary treatment. Additionally, the modified DFs exhibited improved thermal stability, increased absorption peaks in the infrared spectra, decreased crystallinity, improved glucose and cholesterol adsorption ability, and delayed glucose adsorption. The cucumber pomace-derived modified DFs can be used as a functional food additive in bakery, meat, dairy products, and beverages, and their effective use can further enhance the economic benefits.

Effect of leisure activity on frailty trajectories among Chinese older adults: a 16-year longitudinal study.

BACKGROUND: While the significant association between leisure activities and frailty risk among older adults is well-established, the impact of integrated leisure activity scores and different categories of them on frailty trajectories over time remains unclear. METHODS: This study utilized longitudinal data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which enrolled participants aged 65 years and older between 2002 and 2018. Frailty trajectories were derived using group-based trajectory modelling, and based on these trajectories, subjects were classified into various categories. Leisure activity was measured by integrated scores as well as three distinct categories: physically, cognitively, and socially stimulating activity. The effect of leisure activity on frailty trajectories was examined using multinomial logistic regression. RESULTS: By analysing data from 2,299 older adults, three frailty trajectories were identified: non-frail, moderate progressive, and high progressive. The results indicated that an increase in the score of integrated leisure activity was associated with 11% (odds ratio [OR] 0.89; 95% Confidence Interval [CI] 0.85-0.93) and 14% (OR 0.86; 95% CI 0.80-0.91) decrease in the likelihood of being in the moderate and high progressive frailty trajectories, respectively. Engaging in physically stimulating activity lowered the odds of belonging to the moderate and high progressive trajectory by 43% (OR 0.57; 95% CI 0.40-0.81; OR 0.57; 95% CI 0.36-0.92, respectively). Participation in socially stimulating activity showed a lower odd of being in the moderate progressive trajectory (OR 0.68; 95% CI 0.49-0.93) and the high progressive trajectory (OR, 0.61; 95% CI, 0.39-0.95). The effects of leisure activities on frailty trajectories were observed not to vary by age, education level and retirement status. CONCLUSIONS: This study suggests that older adults should be encouraged to increase both the amount and variety of their leisure activities. Physically stimulating activities should be considered the primary choice, followed by socially and cognitively stimulating activities.

Cohesive energy discrepancy drives the fabrication of multimetallic atomically dispersed materials for hydrogen evolution reaction.

Atomically dispersed single atom (SA) and atomic cluster (AC) metallic materials attract tremendous attentions in various fields. Expanding monometallic SA and AC to multimetallic SA/AC composites opens vast scientific and technological potentials yet exponentially increasing the synthesis difficulty. Here, we present a general energy-selective-clustering methodology to build the largest reported library of carbon supported bi-/multi-metallic SA/AC materials. The discrepancy in cohesive energy results into selective metal clustering thereby driving the symbiosis of multimetallic SA or/and AC. The library includes 23 bimetallic SA/AC composites, and expanded compositional space of 17 trimetallic, quinary-metallic, septenary-metallic SA/AC composites. We chose bimetallic M1SAM2AC to demonstrate the electrocatalysis utility. Unique decoupled active sites and inter-site synergy lead to 8/47 mV overpotential at 10 mA cm-2 for alkaline/acidic hydrogen evolution and over 1000 h durability in water electrolyzer. Moreover, delicate modulations towards composition and configuration yield high-performance catalysts for multiple electrocatalysis systems. Our work broadens the family of atomically dispersed materials from monometallic to multimetallic and provides a platform to explore the complex composition induced unconventional effects.

An Internet-Based Developmental Home Care Support Program Improved Maternal Psychological Symptoms and Infant Growth: A Randomized Controlled Trial.

OBJECTIVE: To examine the effects of an internet-based Developmental Home Care Support program (DHCSP) to reduce maternal psychological symptoms and improve preterm infants' physical growth outcomes. METHODS: A randomized controlled trial was conducted. The mother-infant dyads (nm = 34, np = 40) were randomly assigned to either the DHCSP intervention group or the control group. Data were collected at discharge (T0), 1-month corrected age (T1), and 2-month follow-up (T2), including mothers' postpartum depressive and posttraumatic stress disorder (PTSD) symptoms and mother-proxy infants' body length, weight, and head circumference. RESULTS: There were no significant differences in sociodemographic characteristics between the 2 groups at T0, except for mothers' age and monthly household income (both P = .01). Mothers in the DHCSP group reported significantly higher decreases in depression symptoms (ß = -2.24; 95% confidence interval [CI], -4.31 to -0.16, P = .03), and their preterm infants showed significantly more increases in body length (ß = 2.09; 95% CI, 0.30-3.87, P = .02) than the control participants at T2. The 2 groups did not show significant differences in mothers' PTSD symptoms or infants' body weight and head circumference. CONCLUSION: The internet-based DHCSP intervention was effective in improving mothers' depressive symptoms and infants' body length.

Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation.

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.

Caveolin-1 modulates cisplatin sensitivity in oral squamous cell carcinoma through ferroptosis.

OBJECTIVE: Cisplatin-based chemotherapy is widely used for the treatment of oral squamous cell carcinoma (OSCC), but drug resistance and decreased sensitivity often occur during the treatment, greatly weakening its therapeutic effect. Caveolin-1 (CAV1), a protein related to ferroptosis, is involved in regulating the resistance and sensitivity of various tumor chemotherapies. This study aims to investigate whether CAV1 can regulate the sensitivity of OSCC to cisplatin through ferroptosis. METHODS: Through bioinformatics analysis, we analyzed the expression of CAV1 in OSCC and its impact on prognosis analyzed the relationship between CAV1 and tumor immune infiltration, and verified the expression of CAV1 in OSCC through immunohistochemistry experiments. We silenced the expression of CAV1 in OSCC cells through lentiviral transfection and evaluated the cell migration and invasion abilities through wound healing and Transwell assays, respectively. CCK8 assay was used to assess the sensitivity of cells to cisplatin, and ferroptosis-related biochemical marker changes were measured. Western blot was performed to detect the expression of ferroptosis-related proteins. RESULTS: The results revealed a high expression of CAV1 in OSCC, and its high expression predicted poor prognosis in OSCC. CAV1 is associated with drug metabolism pathways in OSCC, and its expression affects the infiltration levels of various immune cells in tumors. Further experiments indicated that CAV1 can inhibit ferroptosis and cisplatin sensitivity in cancer cells, promoting their migration and invasion. CONCLUSION: CAV1 promotes the progression of OSCC and can affect the sensitivity of cisplatin by regulating cellular ferroptosis.

Discovering Native Ant Species with the Potential to Suppress Red Imported Fire Ants.

Native ants have long been considered for their potential to suppress the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), a highly invasive and destructive species. However, the knowledge in this field is limited to behavioral observations of a few related native ants. In this study, by setting up a series of ant combinations of three native ants, i.e., Monomorium chinense Santschi, the robust crazy ant Nylanderia bourbonica Forel, and Iridomyrmex anceps Roger, with S. invicta, we observed the aggression levels and mortality rates. Using baited vials, we also investigated the abundance of native ants in four types of habitats in Eastern China that are preferred by S. invicta (woodland, green belts on roadsides, grassland, and farmland), as well as their seasonal abundance when co-existing with S. invicta and their spatial distribution before and after control of S. invicta. We found that M. chinense and N. bourbonica show a degree of aggression towards S. invicta and can kill substantial proportions of S. invicta under laboratory conditions, but I. anceps does not. Both M. chinense and N. bourbonica can occur in each type of habitat investigated and are more abundant in green belts (particularly lawns with turf) and grasslands relative to other habitats. In grasslands with S. invicta, M. chinense maintained a low density before early July; however, its abundance increased thereafter and reached a peak in September. N. bourbonica also had a low density early in the season and increased steadily from April. Its abundance began to decrease substantially from November. In grasslands invaded by S. invicta, both M. chinense and N. bourbonica were restricted to sites close to the margins before S. invicta was controlled; however, they spread to a larger range within a few weeks after control of S. invicta. In conclusion, M. chinense and N. bourbonica have the potential to suppress S. invicta invasion in habitats that are abundant with these two native ants.

Identification of an arabinogalactan with special structure from Moringa Oleifera leaf and exploration of its immunomodulatory activity.

Arabinogalactan exhibits many biological activities, which is the candidate for functional food ingredients. However, there is limited research on the arabinogalactan from Moringa Oleifera leaf, and its structure needs to be more accurately characterized. This study investigated structural characteristics and immunomodulatory activity of a high-purity polysaccharide from Moringa oleifera leaf (i.e. MOLP-PE) to further explore arabinogalactan from Moringa Oleifera leaf and its potential application area. The results showed that MOLP-PE was a unique type II arabinogalactan: the main chain consisted of → 3, 4)-α-D-Galp-(1→, →3)-ß-D-Galp-(1→ and →2, 4)-ß-D-Rhap-(1→, with branches at the C-4 position of →3, 4)-α-D-Galp-(1→ and →2, 4)-ß-D-Rhap-(1→, consisting of →5)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →6)-ß-D-Galp-(1→ and →4)-ß-D-GalpA-(1→. Compared with arabinogalactan from larch, galactan and arabinan, MOLP-PE exhibited stronger ability in stimulating proliferation, phagocytosis and cytokines release of macrophages and bound with Toll-like receptor 4 closer via more binding sites, which might be due to its higher contents of 1,3-linked-Galp and 1,5-linked-Araf. These findings elucidated that MOLP-PE, as type II arabinogalactan with a unique structure, could be exploited as an immunomodulatory food ingredient.

Diatomic Iron with a Pseudo-Phthalocyanine Coordination Environment for Highly Efficient Oxygen Reduction over 150,000 Cycles.

Atomically dispersed Fe-N-C catalysts emerged as promising alternatives to commercial Pt/C for the oxygen reduction reaction. However, the majority of Fe-N-C catalysts showed unsatisfactory activity and durability due to their inferior O-O bond-breaking capability and rapid Fe demetallization. Herein, we create a pseudo-phthalocyanine environment coordinated diatomic iron (Fe2-pPc) catalyst by grafting the core domain of iron phthalocyanine (Fe-Nα-Cα-Nß) onto defective carbon. In situ characterizations and theoretical calculation confirm that Fe2-pPc follows the fast-kinetic dissociative pathway, whereby Fe2-pPc triggers bridge-mode oxygen adsorption and catalyzes direct O-O radical cleavage. Compared to traditional Fe-N-C and FePc-based catalysts exhibiting superoxo-like oxygen adsorption and an *OOH-involved pathway, Fe2-pPc delivers a superior half-wave potential of 0.92 V. Furthermore, the ultrastrong Nα-Cα bonds in the pPc environment endow the diatomic iron active center with high tolerance for reaction-induced geometric stress, leading to significantly promoted resistance to demetallization. Upon an unprecedented harsh accelerated degradation test of 150,000 cycles, Fe2-pPc experiences negligible Fe loss and an extremely small activity decay of 17 mV, being the most robust candidate among previously reported Fe-N-C catalysts. Zinc-air batteries employing Fe2-pPc exhibit a power density of 255 mW cm-2 and excellent operation stability beyond 440 h. This work brings new insights into the design of atomically precise metallic catalysts.

Targeting PDHK1 by DCA to restore NK cell function in hepatocellular carcinoma.

Pyruvate dehydrogenase complex is a crucial enzyme involved in the oxidation of glucose. It is regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Studies have demonstrated that pyruvate dehydrogenase kinase 1 (PDHK1), a key enzyme in glucose metabolism, behaves like oncogenes. It is highly expressed in tumors and is associated with poor patient prognosis. However, there is limited research on how PDHK1 affects immune cell function. We have established a model of natural killer (NK) cell exhaustion to investigate the impact of dichloroacetate (DCA) on NK cell function. The production of Granzyme B, IFN-γ, TNF-α, and CD107a by NK cells was explored by flow cytometry. The real-time live cell imaging system was used to monitor the ability of NK cells against tumor cells. The Seahorse analyzer was utilized to measure the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of NK cells. The mouse model was used to investigate the potential of combining DCA with adjuvant NK cell infusion. Our study demonstrated that the hepatocellular carcinoma (HCC) microenvironment mediated NK cellular exhaustion, high expression of PDHK1 and reduced cytokine secretion. We discovered that the PDHK1 inhibitor DCA enhances the activity and function of exhausted NK cells infiltrating the tumor microenvironment. Furthermore, in a subcutaneous HCC mouse model, DCA combined with NK cell treatment resulted in retarding cancer progression. This study indicates the potential of DCA in rescuing NK cell exhaustion and eliciting anti-tumor immunity.

Application progress of deep generative models in de novo drug design.

The deep molecular generative model has recently become a research hotspot in pharmacy. This paper analyzes a large number of recent reports and reviews these models. In the central part of this paper, four compound databases and two molecular representation methods are compared. Five model architectures and applications for deep molecular generative models are emphatically introduced. Three evaluation metrics for model evaluation are listed. Finally, the limitations and challenges in this field are discussed to provide a reference and basis for developing and researching new models published in future.

Colonoscopy Training on Virtual-Reality Simulators or Physical Model Simulators: A Randomized Controlled Trial.

OBJECTIVE: This study employed a randomized controlled trial to assess the efficacy of virtual-reality (VR) simulators and physical model simulators on colonoscopy training to explore the optimal and evidence-based simulation training. DESIGN: Forty participants were divided into 2 groups and randomized as dyads: the VR simulator group and the physical model simulator group. All the participants performed a baseline test through porcine colonoscopy. After a 6 h simulation training, each participant underwent a post-test on a pig after bowel preparation, and the procedures were video-recorded. Both the baseline test and the post-test were blindly assessed by 2 experienced assistant director physicians based on the GAGES-C scoring system. SETTING: Simulation center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai. PARTICIPANTS: Forty surgical residents without colonoscopy experience. RESULTS: Both the VR simulator group and the physical model simulator group improved significantly over the baseline test. The VR simulator group performed significantly better than the physical model simulator group, p=0.042. The participants in both groups expressed a high level of simulator satisfaction. CONCLUSIONS: Novice residents can benefit from both VR simulators and physical model simulators. The VR simulator was shown to be more effective for colonoscopy training. VR simulators were more recommended for novices conducting basic colonoscopy training.

The protective effect of glucose selenol on cadmium-induced testicular toxicity in male rat.

This study aimed to investigate the protective effects of glucose selenol on cadmium (Cd)-induced testicular toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into four groups. Cd was administered orally at a dose of 40 mg/L or in combination with orally administered glucose selenol at doses of 0.15 mg/L and 0.4 mg/L for 30 days. The results showed that sperm quality decreased and testicular tissue was damaged in the Cd group; Glucose selenol significantly attenuated the negative effects by improving sperm quality and reducing testicular damage. Transcriptome sequencing analysis showed that Cd stress affected spermatogenesis, sperm motility, oxidative stress, blood-testis barrier and protein metabolism. Four clusters were obtained using the R Mfuzz package, which clustered highly expressed genes under different administrations, and 36 items were enriched. Notably, protein phosphorylation was enriched in the Cd group and is considered to play a key role in the response to Cd stress. We identified fifty-six target selenium (Se) and Cd co-conversion differentially expressed genes (DEGs), including three genes relating to spermatogenesis (Dnah8, Spata31d1b, Spata31d1c). In addition, the obtained DEGs were used to construct a protein-protein interaction network, co-processed with Se and Cd, and 5 modules were constructed. Overall, the analyses of rat testicular physiology and gene expression levels offer new insights into the reproductive toxicity of Cd in rats, and provide potential application prospects for glucose selenol in alleviating the impact of Cd-induced testicular damage.