Robust Sensory Information Reconstruction and Classification With Augmented Spikes.

Sensory information recognition is primarily processed through the ventral and dorsal visual pathways in the primate brain visual system, which exhibits layered feature representations bearing a strong resemblance to convolutional neural networks (CNNs), encompassing reconstruction and classification. However, existing studies often treat these pathways as distinct entities, focusing individually on pattern reconstruction or classification tasks, overlooking a key feature of biological neurons, the fundamental units for neural computation of visual sensory information. Addressing these limitations, we introduce a unified framework for sensory information recognition with augmented spikes. By integrating pattern reconstruction and classification within a single framework, our approach not only accurately reconstructs multimodal sensory information but also provides precise classification through definitive labeling. Experimental evaluations conducted on various datasets including video scenes, static images, dynamic auditory scenes, and functional magnetic resonance imaging (fMRI) brain activities demonstrate that our framework delivers state-of-the-art pattern reconstruction quality and classification accuracy. The proposed framework enhances the biological realism of multimodal pattern recognition models, offering insights into how the primate brain visual system effectively accomplishes the reconstruction and classification tasks through the integration of ventral and dorsal pathways.

Novel amorphous FeOOH-modified Co9S8 nanosheets with enhanced catalytic activity in oxygen evolution reaction.

Efficient oxygen evolution reaction (OER) is vital for water electrolysis and advanced hydrogen energy production. However, the sluggish kinetics of this reaction require significant overpotentials, leading to high energy consumption. Therefore, developing OER electrocatalysts with exceptional performance and long-term durability is crucial for enhancing the energy efficiency and cost-effectiveness of the hydrogen production process. In this research, novel FeOOH/Co9S8 catalysts were prepared through a two-step hydrothermal reaction followed by one-step electrodeposition on nickel foam for an alkaline OER. The as-obtained catalysts possessed abundant non-homogeneous interfaces between FeOOH and Co9S8 nanosheets, conducive to optimized coordination environments of Fe and Co sites by redistributing interfacial charges. This synergy strengthened the chemisorption of oxygenated intermediates, leading to accelerated reaction kinetics, abundant active sites, and enhanced OER performance. The optimized electrocatalyst FeOOH/Co9S8-15 achieved a current density of 10 mA cm-2 at an overpotential of 248 mV and good stability for over 140 h. This study presents a novel approach for producing compelling and durable alkaline dielectric OER electrocatalysts, which will be helpful in the future manufacturing of advanced energy devices.

Prevalence and correlates of mental disorders among Chinese overseas students during the COVID-19: A multi-regional cross-sectional analysis.

BACKGROUND: The global impact of the COVID-19 pandemic extends beyond physical health, significantly affecting mental health. Chinese overseas students are particularly susceptible to the adverse psychological effects of the pandemic. Understanding the prevalence and correlates of mental disorders in this population is essential for developing targeted interventions and support systems. METHODS: Employing a snowball sampling technique, this study recruited Chinese overseas students from diverse regions. The 50-item Self-evaluation Table was utilized to assess the presence of mental disorders. Descriptive statistics, including percentages, 95% confidence intervals, means, and standard deviations, characterized the survey population. The chi-square test identified disparities among categorical variables, while logistic regression explored risk factors for mental disorders among Chinese overseas students. RESULTS: Out of the total sample size of 10,864 Chinese overseas students, a staggering 7,090 (65.4%) met the diagnostic criteria for mental disorders. Furthermore, the degree of mental disorder varied significantly across different regions (p < 0.001), education levels (p < 0.05), the duration of anti-epidemic measures (p < 0.05), and age (p < 0.05), while no significant differences were observed in terms of gender (p > 0.05). Several risk factors contributing to the mental disorder burden among Chinese overseas students during the pandemic were identified, including the seriousness of the epidemic in their residential area, the apprehension of getting infected, anxieties regarding academic performance, the infection control policies implemented by the host government, preventive measures taken locally to counter the epidemic, and challenges encountered in returning to their home country. CONCLUSION: Given the significant challenges in mental health faced by Chinese overseas students during the COVID-19 crisis, addressing their specific needs and implementing tailored measures is imperative. Future public health emergencies should consider the potential mental disorders and disease risks faced by Chinese overseas students. By providing comprehensive support and targeted interventions, policymakers, educational institutions, and healthcare providers can help mitigate the adverse psychological effects and promote the well-being of this vulnerable population.

Bi-Interlayer Strategy for Modulating NiCoP-Based Heterostructure toward High-Performance Aqueous Energy Storage Devices.

Nickel-cobalt (NiCo) phosphides (NCPs) possess high electrochemical activity, which makes them promising candidates for electrode materials in aqueous energy storage devices, such as supercapacitors and zinc (Zn) batteries. However, the actual specific capacitance and rate capability of NCPs require further improvement, which can be achieved through reasonable heterostructural design and loading conditions of active materials on substrates. Herein, novel hierarchical Bi-NCP heterogeneous structures with built-in electric fields consisting of bismuth (Bi) interlayers (electrodeposited on carbon cloth (CC)) are designed and fabricated to ensure the formation of uniform high-load layered active materials for efficient charge and ion transport. The resulting CC/Bi-NCP electrodes show a uniform, continuous, and high mass loading (>3.5 mg) with a superior capacitance reaching 1200 F g-1 at 1 A g-1 and 4129 mF cm-2 at 1 mA cm-2 combined with high-rate capability and durable cyclic stability. Moreover, assembled hybrid supercapacitors (HSCs), supercapatteries, and alkaline Zn-ion (AZBs) batteries constructed using these electrodes deliver high energy densities of 64.4, 81.8, and 319.1 Wh kg-1, respectively. Overall, the constructed NCPs with excellent aqueous energy storage performance have the potential for the development of novel transition metal-based heterostructure electrodes for advanced energy devices.

Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults especially for females: a cross-sectional study.

BACKGROUND: Oral frailty is reported to increase the risk of new onset of mild cognitive impairment. Whereas, the association of oral frailty with cognition among older adults in both physical frail and non-physical frail status has not been sufficiently explored, and whether there are sex differences in the association is unclear. This study investigated the association of oral frailty and physical frailty with global cognitive function and executive function among older adults, as well as the sex differences in such association. METHODS: This cross-sectional study included 307 participants aged ≥ 60 years old from communities between June 2023 and August 2023, in Nanjing, China. Global cognitive function and executive function were assessed by using the Montreal Cognitive Assessment (MoCA) and Trail Making Tests A (TMT-A), respectively. Oral frailty was identified by the combination of natural tooth, Oral Frailty Index-8 (OFI-8), and oral diadochokinesis. Physical frailty was measured by using Fried phenotype model which contained 5 criteria: unintentional weight loss, weakness, exhaustion, slowness, and low physical activity. Multiple linear regression analyses for overall participants and stratified by sex and presence or absence of physical frailty were performed, respectively, to examine the association between oral frailty and cognitive functions. RESULTS: The median age of participants was 70 years old. The study included 158 (51.5%) females, 53 (17.3%) individuals with physical frailty, and 65 (21.2%) participants with oral frailty. After adjustment, the association between oral frailty and global cognitive function was observed in the physical frailty group (B = -2.67, 95% Confidence Interval [CI]: -5.27 to -0.07, p = 0.045) and the females with physical frailty (B = -4, 95% CI: -7.41 to -0.58, p = 0.024). Oral frailty was associated with executive function in overall participants (B = 0.12, 95% CI: 0.01 to 0.22, p = 0.037), physical frailty group (B = 23.68, 95% CI: 1.37 to 45.99, p = 0.038). In the adjusted models, oral frailty was significantly associated with executive function in all females (B = 0.21, 95% CI: 0.05 to 0.36, p = 0.009), in females without physical frailty (B = 0.19, 95% CI: 0.02 to 0.36, p = 0.027), and in females with physical frailty (B = 48.69, 95% CI: 7.17 to 90.21, p = 0.024). CONCLUSIONS: Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults, particularly among females. It is ponderable to consider sex differences and facilitate the management of physical frailty when it comes to promoting cognitive health based on the perspective of oral health among older adults.

Weight loss, glycolipid profile changes in type 2 diabetes patients after esophagectomy: a propensity score matching analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common co-morbidity in patients who receive esophagectomy and has unfavorable effects on glucose and lipid metabolism in patients. This study examines how weight and glycolipid metabolism change in patients with T2DM following esophagectomy. METHODS: This retrospective, one-center, observational analysis with a propensity score matching analysis (PSM) included 114 patients who underwent esophageal surgery in the Department of Cardiothoracic Surgery, the 900th Hospital of Joint Logistic Support Force from 2017 to 2020, which were separated into T2DM group and Non-T2DM group. Weight, body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured and analyzed before and after the operation. RESULTS: Two groups showed similar reductions in weight and BMI after surgery. In the T2DM group, weight decreased from 63.10(10.31) before surgery to 55.10(11.60) kg at 6 months (P < 0.001) with BMI decreasing from 22.67 (2.90) to 19.77 (3.48); While in the Non-T2DM group, weight decreased from 61.42 (8.46) to 53.19 (9.26) kg at 6 months after surgery with BMI decline from 22.49 (2.77) before operation to 19.45 (3.08) at 6 months after surgery. Fasting plasma glucose levels showed a significant decrease (P = 0.035) in the T2DM group at a six-month point of 7.00 (2.21) mmol/L compared to preoperative levels of 7.67 (2.32) mmol/L. HDL levels increased significantly in the Non-T2DM group at six months postoperatively at 1.52 (0.05) with P < 0.001 compared to preoperative levels of 1.22(0.04) mmol/L. TG, LDL, and TC levels decreased significantly in both groups from the preoperative to the 6-month point. CONCLUSIONS: Esophagectomy induces weight loss in T2DM and Non-T2DM groups, improves long-term glucose metabolism in the T2DM group, and enhances lipid metabolism in both groups. Further research is needed to understand their mechanisms.

Effect of oesophagectomy on lipid profiles in patients with oesophageal cancer combined with hyperlipidaemia: a retrospective study.

BACKGROUND: Surgery is widely regarded as a pivotal therapeutic approach for treating oesophageal cancer, and clinical observations have revealed that many oesophageal cancer patients also present with concomitant hyperlipidaemia. It is surprising that few studies have been performed to determine how blood lipid levels are affected by oesophageal cancer resection. This research was designed to assess the influence of oesophageal cancer resection on lipid profiles among individuals diagnosed with both oesophageal cancer and hyperlipidaemia. METHODS: A retrospective analysis was carried out on 110 patients with hyperlipidaemia and oesophageal cancer who had undergone oesophagectomy at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Preoperative and postoperative serological data were collected at seven-, thirty-, sixty-day-, and one-year-long intervals. Changes in lipid levels were compared, the remission of various types of hyperlipidaemia was statistically assessed, and Pearson correlation was used to analyse the association between lipid changes and preoperative body weight. The research sought to assess the reduction in body weight and the proportion of body weight lost one year following surgery. RESULTS: Noteworthy decreases were observed in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with TC decreasing from 6.20 mmol/L to 5.20 mmol/L, TG decreasing from 1.40 mmol/L to 1.20 mmol/L, and LDL decreasing from 4.50 mmol/L to 3.30 mmol/L. Conversely, there was a notable increase in high-density lipoprotein (HDL) levels, which increased from 1.20 mmol/L to 1.40 mmol/L (P < 0.05) compared to the preoperative levels. Notably, the remission rates for mixed hyperlipidaemia (60.9%) and high cholesterol (60.0%) were considerably greater than those for high triglycerides (16.2%). Alterations in TC at one year postoperatively correlated with preoperative weight and weight loss (r = 0.315, -0.216); changes in TG correlated with preoperative weight, percentage of total weight loss (TWL%), and weight reduction (r = -0.295, -0.246, 0.320); and changes in LDL correlated with preoperative weight, TWL%, and weight loss (r = 0.251, 0.186, and -0.207). Changes in non-high-density lipoprotein(non-HDL) were linked to preoperative weight (r = 0.300), and changes in TG/HDL were correlated with preoperative weight and TWL% (r = -0.424, -0.251). CONCLUSIONS: Oesophagectomy significantly improved lipid profiles in oesophageal cancer patients, potentially leading to a reduction in overall cardiovascular risk.

Isolation, identification, and optimization of conditions for the degradation of four sulfonamide antibiotics and their metabolic pathways in Pseudomonas stutzeri strain DLY-21.

Overuse of sulfonamides in aquaculture and agriculture leads to residual drugs that cause serious pollution of the environment. However, the residues of sulfonamides in the environment are not unique, and the existing microbial degradation technology has a relatively low degradation rate of sulfonamides. Therefore, in this study, a Pseudomonas stutzeri strain (DLY-21) with the ability to degrade four common SAs was screened and isolated from aerobic compost. Under optimal conditions, the DLY-21 strain degraded four sulfonamides simultaneously within 48 h, and the degradation rates were all over 90%, with the average degradation rates of SAs being sulfoxide (SDM) ≈ sulfachloropyridazine (SCP) > sulfa quinoxaline (SQ) > sulfadiazine (SQ). In addition, the main compounds of the strain DLY-21-degrading SAs were identified by LC-MS analysis. On this basis, four detailed reaction pathways for SA degradation were deduced. This is the first report of the use of a P. stutzeri strain to degrade four sulfonamide antibiotics (SQ, SDM, SCP, and SM1), which can improve the removal efficiency of sulfonamide antibiotic pollutants and thus ameliorate environmental pollution. The results showed that DLY-21 had a good degradation effect on four SAs (SQ, SDM, SCP, and SM1).

Repetitive transcranial magnetic stimulation for Alzheimer's disease: an overview of systematic reviews and meta-analysis.

Objective: Alzheimer's disease (AD) is a prevalent neurodegenerative condition that significantly impacts both individuals and society. This study aims to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for AD by summarizing the evidence from systematic reviews (SRs) and meta-analyses (MAs). Methods: SRs/MAs of rTMS for AD were collected by searching Embase, Web of Science, Cochrane Library, PubMed, CNKI, VIP, Sino-Med, and Wanfang databases. The search was conducted from database creation to January 23, 2024. Methodological quality, reporting quality and risk of bias were assessed using the Assessing Methodological Quality of Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS) tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In addition, the quality of evidence for outcome measures was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Eight SRs/MAs included in this study met the inclusion criteria. Based on the AMSTAR-2, 4 of the SRs/MA were classified as low quality, while the remaining 4 were deemed to be of very low quality. The PRISMA analysis revealed that out of the 27 items reporting, 16 achieved full reporting (100%). However, there were still some deficiencies in reporting, particularly related to protocol and registration, search strategy, risk of bias, and additional analysis. The ROBIS tool indicated that only 3 SRs/MAs had a low risk of bias. The GRADE assessment indicated that 6 outcomes were of moderate quality (18.75%), 16 were of low quality (50%), and 10 were classified as very low quality (31.25%). Conclusion: Based on the evidence collected, rTMS appears to be effective in improving cognitive function in AD patients, although the methodological quality of the SRs/MAs reduces the reliability of the conclusions and the overall quality is low. However, based on the available results, we still support the value of rTMS as an intervention to improve cognitive function in AD. In future studies, it is necessary to confirm the efficacy of rTMS in AD patients and provide more reliable and scientific data to contribute to evidence-based medicine.

A coupling model based on spatial characteristics and evolution of terrestrial ecosystem carbon storage: a case study of Hanzhong.

Ecosystem carbon storage (ECS) is a critical consideration in reducing the impact of global warming and tackling environmental challenges, positioning it at the forefront of contemporary research. Due to the significant differences in the influence of land usage patterns on ECS in various policy contexts and China's commitment to attaining a carbon-neutral status, a model simulating different scenarios is needed to analyze the spatiotemporal characteristics and evolutionary process of carbon storage in terrestrial ecosystems accurately. To address this challenge, this study established a coupling model of "Geographical analysis -Evolution analysis -Predicting (GEP)" for assessing ecosystem ECS and analyzing its spatial characteristics and evolutionary patterns and projecting the spatial distribution of ECS under various developmental scenarios, which analyzed variations in ECS across different levels of magnitude and delineated the changing areas across a range of varying scenarios in the future additionally. The outcomes suggested that the ECS decreased by 1.17 × 106 t from 1990 to 2020, which pertaining to the utilization transfer of land in the area, whose change in ECS levels with a positive trend. It is predicted that the ECS will grow by 1.15 × 106 t and 1.44 × 106 t, in 2030 and 2060 compared with 2020 within the framework of natural development scenario (NDS), while within the framework of ecological protection scene (EPS), ECS will increase significantly, increasing by 3.06 × 106 t and 4.44 × 106 t. There will be more areas where ECS increases within the framework of EPS, by comparing with the NDS. This study offers a comprehensive analysis of Hanzhong City's carbon storage trends, demonstrating its significant impact on climate change mitigation and serving as a predictive model for similar regions, which underscores the importance of localized carbon management strategies, offering valuable insights for local governments in formulating effective climate adaptation and mitigation policies.

Supertwisted Chiral Gyroid Mesophase in Chiral Rod-Like Compounds.

Among the intriguing bicontinuous self-assembled structures, the gyroid cubic is the most ubiquitous. It is found in block and star polymers, surfactants with or without solvent, in thermotropic liquid crystals with end- or side-chains, and in biosystems providing structural color and modelling cell mitosis. It contains two interpenetrating networks of opposite chirality and is thus achiral if, as usual, the content of the two nets is the same. However, we now find that this is not the case for strongly chiral compounds. While achiral molecules follow the opposite twists of nets 1 and 2, molecules with a chiral center in their rod-like core fail to follow the 70° twist between junctions in net 2 and instead wind against it by -110° to still match the junction orientation. The metastable chiral gyroid is a high-entropy high-heat-capacity mesophase. The homochirality of its nets makes the CD signal of the thienofluorenone compounds close to that in the stable I23 phase with 3 isochiral nets.

Highly Ordered Gyroid Nanostructured Polymers: Facile Fabrication by Polymerizable Pluronic Surfactants.

Highly ordered, network-nanostructured polymers offer compelling geometric features and application potential. However, their practical utilization is hampered by the restricted accessibility. Here, we address this challenge using commercial Pluronic surfactants with a straightforward modification of tethering polymerizable groups. By leveraging lyotropic self-assembly, we achieve facile production of double-gyroid mesophases, which are subsequently solidified via photoinduced cross-linking. The exceptionally ordered periodicities of Ia3d symmetry in the photocured polymers are unambiguously confirmed by synchrotron small-angle X-ray scattering (SAXS), which can capture single-crystal-like diffraction patterns. Electron density maps reconstructed from SAXS data complemented by transmission electron microscopy analysis further elucidate the real-space gyroid assemblies. Intriguingly, by tuning the cross-linking through thiol-acrylate chemistry, the mechanical properties of the polymer are modulated without compromising the integrity of Ia3d assemblies. The 3-D percolating gyroid nanochannels demonstrate an ionic conductivity that surpasses that of disordered structures, offering promising prospects for scalable fabrication.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Discrimination of untreated and sodium sulphite treated bean sprouts by Fourier transform infrared spectroscopy and chemometrics.

Sprouts of black beans (Phaseolus vulgaris L.), soybeans (Glycine max L.) and mung beans (Vigna radiata L.) are widely consumed foods containing abundant nutrients with biological activities. They are commonly treated with sulphites for the preservation and extension of shelf-life. However, our previous investigation found that immersing the bean sprouts in sulphite might convert the active components into sulphur-containing derivatives, which can affect both the quality and safety of the sprouts. This study explores the use of FTIR in conjunction with chemometric techniques to differentiate between non-immersed (NI) and sodium sulphite immersed (SI) black bean, soybean and mung bean sprouts. A total of 168 batches of raw spectra were obtained from NI and SI-bean sprouts using FTIR spectroscopy. Four pre-processing techniques, three modelling assessment techniques and four model evaluation indices were examined for differences in performance. The results show that the multiplicative scatter correction is the most effective pre-processing method. Among the models, the accuracy rate of the three models was as follows: radial basis function neural network (95%) > convolutional neural network (91%) > random forest (82%). The overall findings indicate that FTIR spectroscopy, in conjunction with appropriate chemometric approaches, has a high potential for rapidly determining the difference between NI and SI-bean sprouts.

Sleep factors were associated with a higher risk of MAFLD and significant fibrosis.

PURPOSE: The relationships of sleep factors separately and jointly with metabolic associated fatty liver disease (MAFLD) and significant fibrosis remain unclear. We intended to explore the relationships in the United States. METHODS: This cross-sectional study included 4477 individuals from the National Health and Nutrition Examination Survey from 2017 to 2018. Information regarding each sleep factor (sleep duration, trouble sleeping, snoring, excessive daytime sleep, and sleep apnea symptoms) was obtained through questionnaires. MAFLD was diagnosed by transient elastography according to the consensus definitions. Multivariable logistic regression models were employed to explore relationships of sleep factors separately and jointly with MAFLD and significant fibrosis. RESULTS: Participants having a poor sleep pattern was associated with higher MAFLD and significant fibrosis risk, and poor sleep pattern was related to about threefold (OR, 3.67; 95% CI, 1.82-7.37) increased risk of MAFLD remarkably. When examining specific factors of sleep patterns individually, trouble sleeping (OR, 1.53; 95% CI, 1.10-2.12), snoring (OR, 2.11; 95% CI, 1.40-3.19), excessive daytime sleep (OR, 1.57; 95% CI, 0.93-2.62), and sleep apnea symptoms (OR, 1.87; 95% CI, 1.13-3.10) were positively associated with the odds of MAFLD (all P < 0.05). However, sleep duration was not independently correlated with MAFLD or significant fibrosis. Sleep patterns showed similar relationships with MAFLD, regardless of all age, sex, physical activity, and shift work groups. CONCLUSIONS: Poor sleep pattern was linked with a considerably higher risk of MAFLD and significant fibrosis.

Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases.

HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4-de]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4-de]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib. Rat studies showed that 8a and 9a with the newly developed core have good pharmacokinetic properties with an oral bioavailability of 41.7 and 42.0%, respectively. Oral administration of 4a and 10e (30 mg/kg, QD) displayed significant antitumor efficacy in an in vivo xenograft model. We proposed promising strategies for the development of HER2insYVMA mutant inhibitors in this study.

Independent and joint association of physical activity and adequate weekday sleep duration with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: The independent and joint association of physical activity (PA) and weekday sleep duration with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. AIMS: We intended to explore this association in the United States. METHODS: This cross-sectional study recruited 4974 individuals from the National Health and Nutrition Examination Survey between 2017 and 2018. Information regarding PA and weekday sleep duration was obtained through questionnaires. Metabolic associated fatty liver disease (MAFLD) was diagnosed by transient elastography based on the consensus definitions. Multivariable logistic regression models were employed to investigate the independent and joint association of PA and weekday sleep duration with MAFLD. RESULTS: Of the 4974 subjects, engaging in active PA or sustaining adequate sleep duration was associated with decreased the odds of MAFLD (p < 0.05). Specifically, active leisure-time PA was linked to lower 37 % odds of MAFLD (OR, 0.63; 95 % CI, 0.55-0.73). Individuals who had one to twice times (150-299 min/week) or more than twice (≥300 min/week) the recommended amount of leisure-time PA by PA Guidelines had 19 % (OR, 0.81; 95 % CI, 0.67-0.99) and 45 % (OR, 0.55; 95 % CI, 0.47-0.65) lower odds of MAFLD, respectively (P for trend <0.001). Individuals with adequate weekday sleep duration was associated with 24 % lower odds of MAFLD (OR, 0.76;95 % CI,0.67-0.88). Notably, active PA combined with adequate weekday sleep duration significantly decreased the odds ratios for MAFLD by 35 % (OR: 0.65, 95 % CI, 0.52-0.80). However, in individuals with significant alcohol use, the joint effect of total PA and weekday sleep duration on MAFLD was not statistically significant. CONCLUSIONS: Both active PA and adequate weekday sleep duration were inversely associated with the risk of MASLD independently, while combining them could further lower the risk of MASLD.

High-throughput mutagenesis and screening approach for the identification of drug-resistant mutations in the rifampicin resistance-determining region of mycobacteria.

Rifampicin is the most powerful first-line antibiotic for tuberculosis, which is caused by Mycobacterium tuberculosis. Although accumulating evidence from sequencing data of clinical M. tuberculosis isolates suggested that mutations in the rifampicin-resistance-determining region (RRDR) are strongly associated with rifampicin resistance, the comprehensive characterisation of RRDR polymorphisms that confer this resistance remains challenging. By incorporating I-SceI sites for I-SceI-based integrant removal and utilizing an L5 swap strategy, we efficiently replaced the integrated plasmid with alternative alleles, making mass allelic exchange feasible in mycobacteria. Using this method to establish a fitness-related gain-of function screen, we generated a mutant library that included all single-amino-acid mutations in the RRDR, and identified the important positions corresponding to some well-known rifampicin-resistance mutations (Q513, D516, S522, H525, R529, S531). We also detected a novel two-point mutation located in the RRDR confers a fitness advantage to M. smegmatis in the presence or absence of rifampicin. Our method provides a comprehensive insight into the growth phenotypes of RRDR mutants and should facilitate the development of anti-tuberculosis drugs.

Pure optical twist with zero net torque.

In photonic systems, bilayer or multilayer systems exhibit numerous exciting phenomena induced by twisting. Thus, it is highly desired to explore the twisting effect by engineering the light-matter interactions. Optical torque, an important means in optical micromanipulation, can rotate micro-objects in various ways, enabling a wide range of promising applications. In this study, we present an interesting phenomenon called "pure optical twist" (POT), which emerges when a bilayer structure with specific symmetry is illuminated by counter-propagating lights with opposite spin and/or orbital angular momentum. Remarkably, this leads to zero net optical torque but yet possesses an interesting mechanical effect of bilayer system twisting. The crucial determinant of this phenomenon is the rotational symmetries of each layer, which govern the allowed azimuthal channels of the scattered wave. When the rotational symmetries do not allow these channels to overlap, no resultant torque is observed. Our work will encourage further exploration of the twisting effect through engineered light-matter interactions. This opens up the possibility of creating twisted bilayer systems using optical means, and constructing a stable bilayer optical motor that maintains identical rotation frequencies for both layers.

Injectable and Thermosensitive Hydrogel with Platelet-Rich Plasma for Enhanced Biotherapy of Skin Wound Healing.

The rapid and effective healing of skin wounds resulted from severe injuries and full-layer skin defects remains a pressing clinical challenge in contemporary medical practice. The reduction of wound infection and rapid healing is helpful to rebuild and repair skin tissue. Here, a thermosensitive chitosan-based wound dressing hydrogel incorporating ß-glycerophosphate (GP), hydroxy propyl cellulose (HPC), graphene oxide (GO), and platelet-rich plasma (PRP) is developed, which exhibits the dual functions of antibacterial properties and repair promotion. GP and HPC enhance the mechanical properties through forming hydrogen bonding connection, while GO produces local heat under near-infrared light, leading to improved blood circulation and skin recovery. Notably, antibacterial properties against Pseudomonas aeruginosa, and control-release of growth factors from PRP are also achieved based on the system. In vitro experiments reveal its biocompatibility, and ability to promote cell proliferation and migration. Animal experiments demonstrate that the epithelial repair and collagen deposition can be promoted during skin wound healing in Sprague Dawley rats. Moreover, a reduction in wound inflammation levels and the improvement of wound microenvironment are observed, collectively fostering effective wound healing. Therefore, the composite hydrogel system incorporated with GO and PRP can be a promising dressing for the treatment of skin wounds.