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Abstract Background Chronic lymphocytic leukemia (CLL) is one of the most frequent occurring types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. At present, the molecular mechanism driving the pathogenesis and progression of CLL is not fully understood. The protein Synaptotagmin 7 (SYT7) encoded by the SYT7 gene has been found to be closely related to the development of various solid tumors, but its role in CLL is unclear. In this study, we investigated the function and molecular mechanism of SYT7 in CLL. Methods The expression level of SYT7 in CLL was determined by immunohistochemical staining and qPCR. The role of SYT7 in promoting CLL development was verified by in vivo and in vitro experiments. The molecular mechanism of SYT7 in CLL was elucidated by methods such as GeneChip analysis and Co-immunoprecipitation assay. Results Malignant behaviors such as proliferation, migration, and anti-apoptosis of CLL cells were significantly inhibited after SYT7 gene knockdown. In contrast, SYT7 overexpression promoted CLL development in vitro. Consistently, the knockdown of SYT7 also inhibited xenograft tumor growth of CLL cells. Mechanistically, SYT7 promoted CLL development by inhibiting SYVN1-mediated KNTC1 ubiquitination. The KNTC1 knockdown also attenuated the effects of SYT7 overexpression on development of CLL. Conclusions SYT7 regulates the progression of CLL through SYVN1-mediated KNTC1 ubiquitination, which has potential value for molecular targeted therapy of CLL.

Objective: To compare the clinical practicability of two bleeding grading systems (BGS) in pregnancy with Immune Thrombocytopenia (ITP). Methods: The clinical data of 154 cases were retrospectively analyzed with the 2016 version of the ITP Bleeding Scale (ITP-2016) and the ITP-specific bleeding assessment tool (ITP-BAT). The correlation between the two BGS and the relations among the platelet counts, gestational ages, and disease stages were respectively analyzed. Results: There is no significant difference between the two BGS in the patients’ ages, nor between the newly diagnosed and the persistent group or the chronic group, while the difference between the persistent and the chronic group was significant ( P = 0.001; P = 0.001). There is a negative correlation between the bleeding grade and platelet count (r = -0.436; r = -0.390), while the correlation between the two BGS was positive (r = 0.921). The proportions of identical scores provided by two different physicians using the two BGS were 94.8% and 93.5%. The difference before and after the treatment were significantly different ( P = 0.013; P = 0.037). It takes less time to score with the ITP-2016 ( P = 0.011). Conclusion: Both systems can be useful for disease evaluations, risk assessments and efficacy evaluations in Chinese pregnant women with ITP. The ITP-2016 takes less time and is more suitable for Chinese pregnant patients with ITP.

The application of pesticides is critical during the growth of high-quality grape for wine making. However, pesticide residues have significant influence on the wine flavor. In this study, gas chromatography-mass spectrometry (GC-MS) was performed and the obtained datasets were analyzed with multivariate statistical methods to investigate changes in flavor substances in wine during fermentation. The principal component analysis (PCA) score plot showed significant differences in the metabolites of wine treated with various pesticides. In trials using five pesticides (hexaconazole, difenoconazole, flutriafol, tebuconazole, and propiconazole), more than 86 metabolites were changed. Most of these metabolites were natural flavor compounds, like carbohydrates, amino acids, and short-chain fatty acids and their derivatives, which essentially define the appearance, aroma, flavor, and taste of the wine. Moreover, the five pesticides added to grape pulp exhibited different effects on the metabolic pathways, involving mainly alanine, aspartate and glutamate metabolism, butanoate metabolism, arginine, and proline metabolism. The results of this study will provide new insight into the potential impact of pesticide residues on the metabolites and sensory profile of wine during fermentation.

Electromagnetic radiation can cause serious harm to the human body, such as the rise in body temperature and the decrease in immune function. In this study, the carbon nanotubes (CNTs)/Fe3O4 nonwovens were used to prepare wearable flexible absorbing materials. First, the single-layer absorbing structures were prepared by hot rolling, dipping, and film fabrication, respectively. Then, the single-layer structures were combined to form the multi-layer absorbing structures. By testing and analyzing the absorbing performance of various structures in the X-band frequency range, the optimum combination scheme was found, together with a good reflection loss value of CNTs/Fe3O4 nonwoven material. The experiment results displayed that the single-layer hot-rolled nonwovens modified by CNTs have the best wave absorbing performance. Its minimum reflection loss of −18.59 dB occurred at 10.55 GHz, and the efficient frequency occurred at 8.86–12.40 GHz. The modified film can significantly improve the absorbing performance of multi-layer structures. In addition, the absorbing performance was closely related to both the place where the absorbing film was introduced and the type of absorbing fillers. When the film-forming CNTs (FC) film was located at the bottom layer of the multi-layer structure, the hot rolled CNTs hot rolled mixed reagent film forming CNTs (HC-HM-FC) structure constructed exhibited the best absorbing effects. Its minimum reflection loss can reach −33 dB, and the effective absorbing frequency range covered half of the X-band.

The essential pigment chlorophyll (Chl) plays important roles in light harvesting and energy transfer during photosynthesis. Here we present the data from a comparative proteomic analysis of chlorophyll-deficient Brassica napus mutant cde1 and its corresponding wild-type using the iTRAQ approach (Pu Chu et al., 2014 [1]). The distribution of length and number of peptides, mass and sequence coverage of proteins identified was calculated, and the repeatability of the replicates was analyzed. A total of 443 differentially expressed proteins were identified in B. napus leaves, including 228 down-accumulated proteins mainly involved in photosynthesis, porphyrin and chlorophyll metabolism, biosynthesis of secondary metabolites, carbon fixation and 215 up-accumulated proteins that enriched in the spliceosome, mRNA surveillance and RNA degradation.

Background: Apigenin is one of the natural flavonoids found mainly in natural plants, as well as some fruits and vegetables, with celery in particular being the most abundant. Apigenin has antioxidant, anti-tumor, anti-inflammatory, and anticancer effects. In this research, we attempted to further investigate the effects of apigenin on the mechanism of repairing oxidative cell damage. The present study hopes to provide a potential candidate for abnormal skin pigmentation disorders. Methods: We used 0.4 mM H2O2 to treat B16F10 cells for 12 h to establish a model of oxidative stress in melanocytes, and then we gave apigenin (0.1~5 μM) to B16F10 cells for 48 h, and detected the expression levels of melanin synthesis-related proteins, dendritic regulation-related proteins, antioxidant signaling pathway- and Nrf2 signaling pathway-related proteins, autophagy, and autophagy-regulated pathways by immunoblotting using Western blotting. The expression levels of PI3K/Akt/mTOR proteins were measured by β-galactosidase staining and Western blotting for cellular decay, JC-1 staining for mitochondrial membrane potential, and Western blotting for mitochondrial fusion- and mitochondrial autophagy-related proteins. Results: Apigenin exerts antioxidant effects by activating the Nrf2 pathway, and apigenin up-regulates the expression of melanin synthesis-related proteins Tyr, TRP1, TRP2, and gp100, which are reduced in melanocytes under oxidative stress. By inhibiting the expression of senescence-related proteins p53 and p21, and delaying cellular senescence, we detected the mitochondrial membrane potential using JC-1, and found that apigenin improved the reduction in mitochondrial membrane potential in melanocytes under oxidative stress, and maintained the normal function of mitochondria. In addition, we further detected the key regulatory proteins of mitochondrial fusion and division, MFF, p-DRP1 (S637), and p-DRP1 (S616), and found that apigenin inhibited the down-regulation of fusion-associated protein, p-DRP1 (S637), and the up-regulation of division-associated proteins, MFF and p-DRP1 (S616), due to oxidative stress in melanocytes, and promoted the mitochondrial fusion and ameliorated the imbalance between mitochondrial division and fusion. We further detected the expression of fusion-related proteins OPA1 and Mitofusion-1, and found that apigenin restored the expression of the above fusion proteins under oxidative stress, which further indicated that apigenin promoted mitochondrial fusion, improved the imbalance between mitochondrial division and fusion, and delayed the loss of mitochondrial membrane potential. Apigenin promotes the expression of melanocyte autophagy-related proteins and the key mitochondrial autophagy proteins BNIP3L/Nix under oxidative stress, and activates the PINK1/Parkin signaling pathway by up-regulating the expression of autophagy-related proteins, as well as the expression of PINK1 and Parkin proteins, to promote melanocyte autophagy and mitochondrial autophagy. Conclusions: Apigenin exerts anti-melanocyte premature aging and detachment effects by promoting melanin synthesis, autophagy, and mitochondrial autophagy in melanocytes, and inhibiting oxidative cell damage and senescence. [ABSTRACT FROM AUTHOR]

Abstract Background Colorectal cancer (CRC) is a common malignant tumor. N6-Methyladenosine (m6A) modification plays an important role in the regulation of glycolysis in tumor cells and may be a potential target for tumor therapy. Methods The role of METTL14, an m6A writer, in CRC was investigated through functional assays including cell viability, colony formation, and glycolysis-related measurements (glucose uptake, lactate production, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR)). The target gene regulated by METTL14 in an m6A-dependent manner was identified using molecular biology techniques. In addition, CRC cells overexpressing METTL14 were subcutaneously injected into mice to verify the regulatory effect of METTL14 on tumor growth in vivo. Results Our data suggested that METTL14 was up-regulated in CRC cell lines, and over-expression of METTL14 suppressed cell proliferation and glycolysis. Meanwhile, ATF2 m6A level was significantly up-regulated by over-expression of METTL14, and the binding relationship between ATF2 and METTL14 was further verified. METTL14-m6A regulated ATF2 in CRC cells participates in the regulation of glycolysis. METTL14 also suppressed tumorigenesis of nude mice. Conclusion Intervention with METTL14 mediated m6A modifications or its associated protein ATF2 may provide new strategies for CRC therapy.

Abstract Background Vitamin deficiency remains a significant global public health issue, especially in pediatric healthcare. This study aimed to access knowledge, attitude, and practice (KAP) of parents from Yangzhou (China) towards vitamin A and D intake in their children. Methods Cross-sectional survey was carried out in Yangzhou, China, between December 2022 and May 2023. Self-designed questionnaire was utilized to gather data on the Knowledge, Attitudes, and Practices (KAP) among parents of children aged between 3 months and 12 years. Results The survey yielded 475 valid responses. The prevalence of vitamin D insufficiency and deficiency was 8.84% and 4.42%, respectively, while vitamin A deficiency was reported in 0.21% of children. The analysis of Knowledge, Attitudes, and Practices (KAP) scores in parents revealed mean values of 4.93 ± 1.92 (with a possible range of 0–13) for Knowledge, 33.73 ± 3.69 (range 10–40) for Attitudes, and 37.07 ± 4.22 (range 10–50) for Practices. Structural Equation Modeling (SEM) confirmed a significant impact of vitamin knowledge on attitudes (β= -0.059, P

Abstract This article analyzes the interference issues between radar and radar, radar and communication, and communication and communication in a vehicle network equipped with a radar communication integrated system. To improve the signal-to-interference-plus-noise ratio (SINR) of radar signals while ensuring communication quality, we provide an optimized expression for the signal-to-noise ratio of radar signals constrained by communication quality. To solve mixed integer nonlinear programming optimization problems, Q-learning algorithm is introduced. In our Q-learning algorithm, based on the action state space established by transmission power and channel resources, the optimization problem is transformed into solving using a reward function. The evaluation results indicate that compared with existing solutions, the proposed algorithm can more effectively improve the total SINR of radar signals and the throughput of communication signals.

Abstract Objective To determine the efficacy and safety of combined low‐dose rituximab with conventional therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) treatment. Methods Total 73 patients with CIDP were enrolled for the retrospective cohort study, and divided into conventional first‐line therapy cohort (n = 40) and combined low‐dose rituximab (100 mg per infusion) cohort (n = 33). The outcome measures include scores of I‐RODS, mRS, INCAT, ONLS, TSS, and COMPASS 31 scale at baseline and regular four visits (4, 16, 28, and 52 weeks), as well as proportion of favorable response and outcome, corticosteroids dosage, and deterioration occurrence during follow‐up. Results Compared to conventional therapy cohort, combined rituximab cohort presented better improvements and higher proportion of favorable response in scales assessments at each visit, as well as significantly reduced corticosteroids dosage and deterioration occurrence during the follow‐up. Analyses of subgroups showed better improvements in both typical CIDP and CIDP variants in combined rituximab cohort than those in conventional therapy cohort, but had no differences between each other. Early initiating combined rituximab regimen (

Abstract The current single-cell analysis technologies such as fluorescence-activated cell sorting (FACS) and fluorescence-activated droplet sorting (FADS) could decipher the cellular heterogeneity but were constrained by low sorting performance and cell viability. Here, an ultra-sensitive single-cell sorting platform has been developed by integrating the FADS technology with Tetramer-HCR-EvaGreen (THE) fluorescence signal amplification. The THE system produced much higher fluorescence signal than that of the single Tetramer or Tetramer-HCR signal amplification. Upon application to target MCF-7 cells, the platform exhibited high efficacy and selectivity while maintaining more than 95% cell viability. The THE-FADS achieved sorting efficiencies of 55.5% and 50.3% with purities of 91% and 85% for MCF-7 cells in PBS solutions and simulated serum samples, respectively. The sorted MCF-7 cells showed similar proliferation together with CK19 and EGFR mRNA expression compared with the control cells. The established THE-FADS showed the promising prospects to cellular heterogeneity understanding and personalized medicine.

Abstract Background To analyze the demographic characteristics of retinopathy of prematurity (ROP) in China, attempting to propose optimized screening criteria and hopefully providing valuable information for future updates to the ROP guideline. Methods A multicenter, retrospective-cohort study was conducted. The study included infants born between January 1, 2018, and July 31, 2023, who underwent ROP screening and were diagnosed with ROP at seven screening centers in China. Examinations were carried out in accordance with the ROP guidelines in 2014: infants with a gestational age (GA)

To tackle the efficiency droop, we employed an epitaxial structure engineering approach and utilized SimuLED software to thoroughly investigate the influence of the quantum barrier (QB) thickness on the performance of Micro-LEDs, and delve into the corresponding carrier transport behavior. The results demonstrate that the effect of QB thickness on the performance of Micro-LEDs is closely related to injection current density. Within the current density range of 0–30 A/cm2, a thicker QB layer leads to a higher internal quantum efficiency (IQE) for Micro-LEDs. Conversely, when the current density is in the range of 30–100 A/cm2, employing a thinner QB layer in the LED structure can yield higher IQE values. In addition, this work suggests that tunneling effects and Quantum Confined Stark Effect (QCSE) dominate at different current densities, resulting in an opposite dependency of IQE on QB thickness. Furthermore, our findings indicate that adjusting QB thickness can significantly affect both the peak external quantum efficiency (EQE) and peak current density of Micro-LEDs.

Abstract Background Pulmonary space-occupying lesions are typical chronic pulmonary diseases that contribute significantly to healthcare resource use and impose a large disease burden in China. A time-series ecological trend study was conducted to investigate the associations between environmental factors and hospitalizations for pulmonary space-occupying lesions in North of China from 2014 to 2022. Methods The DLNM was used to quantify the association of environmental factors with lung cancer admissions. The heating-, age-, gender-, malignancy-specific effects were further estimated to identify the susceptible groups. Results During the study period, fluctuations in air pollutants and climate conditions closely mirrored changes in hospitalizations for pulmonary space-occupying lesions. Totally, the distributed lag surface showed clear positive associations between pulmonary tumor hospitalization and PM2.5 (RRlag30: 1.000912; 95%CI: 1.000076, 1.00175), PM10 (RRlag30: 1.002246; 95%CI: 1.000474, 1.004021), SO2 (RRlag30: 1.002714; 95%CI: 1.001071, 1.004414), CO (RRlag30: 1.002231; 95%CI: 1.000592, 1.003873). Additionally, the associations between air pollutants and hospitalizations for pulmonary space-occupying lesions were significantly stronger during the heating season. Population aged 65 or older, females and those diagnosed with malignancies were more vulnerable for the risk of pulmonary space-occupying lesions diseases due to air pollution exposure. Conclusions The present study illustrated risk and burden for pulmonary space-occupying lesions hospitalization associated with air pollution, especially among population aged ≥ 65, or female.

Abstract Background Active cytomegalovirus (CMV) infection is associated with poor prognosis in septic patients with critical illness. Patients of septic category are highly likely to benefit from prophylactic antiviral therapy. Nevertheless, the clinical characteristics for CMV reactivation are lacking among septic patients requiring mechanical ventilation. The aim of this study was to investigate the incidence, risk factors, and clinical outcomes regarding active CMV infection in mechanically ventilated patients with sepsis. Methods A single-center, retrospective cohort study conducted from January 2021 to December 2023 that included septic patients on mechanical ventilation at the intensive care unit (ICU) of a national hospital. Study participants were divided into active and non-active CMV infection groups based on CMV DNAemia within a 28-day hospitalization period in ICU. Clinical features, laboratory findings, treatment measures, and clinical outcomes were compared between the two groups. Results Among 118 septic patients, 21 (17.8%) exhibited active CMV infection within 28-day ICU admission. Hemoglobin served as an independent risk factor and predictor for active CMV infection (P

Abstract Artificial intelligence (AI), particularly large language models like GPT-4o, holds promise for enhancing diagnostic accuracy in healthcare. This study evaluates the diagnostic performance of GPT-4o compared to human ophthalmologists in glaucoma cases. A prospective, observational study was conducted at a tertiary care ophthalmology center. Twenty-six glaucoma cases, including both primary and secondary types, were selected from publicly available databases and institutional records. The cases were analyzed by GPT-4o and three ophthalmologists with varying levels of experience. The accuracy and completeness of primary and differential diagnoses were assessed using 10-point and 6-point Likert scales, respectively. Statistical analyses were performed using nonparametric methods, including the Kruskal–Wallis and Mann–Whitney U tests. GPT-4o was significantly less accurate in primary diagnosis compared to human ophthalmologists. Specifically, GPT-4o achieved a mean score of 5.500 (p

Abstract Depression-anxiety comorbidity is commonly attributed to the occurrence of specific symptoms bridging the two disorders. However, the significant heterogeneity of most bridging symptoms presents challenges for psychopathological interpretation and clinical applicability. Here, we conceptually established a common bridging factor (cb factor) to characterize a general structure of these bridging symptoms, analogous to the general psychopathological p factor. We identified a cb factor from 12 bridging symptoms in depression-anxiety comorbidity network. Moreover, this cb factor could be predicted using edge-centric connectomes with robust generalizability, and was characterized by connectome patterns in attention and frontoparietal networks. In an independent twin cohort, we found that these patterns were moderately heritable, and identified their genetic connectome-transcriptional markers that were associated with the neurobiological enrichment of vasculature and cerebellar development, particularly during late-childhood-to-young-adulthood periods. Our findings revealed a general factor of bridging symptoms and its neurobiological architectures, which enriched neurogenetic understanding of depression-anxiety comorbidity.

Background/Aims This study aimed to assess the impact of INTERCEPT Foam Spray (IFS) application on delayed endoscope reprocessing through microbiological surveillance culture (MSC). Methods A quasi-experimental, matched-comparison pilot study was conducted using gastrointestinal endoscopy. IFS was applied to the endoscopes after precleaning and before reprocessing the next day. An equal number of endoscopes, matched by endoscope type, were subjected to routine reprocessing. The MSC were subjected to high-level disinfection to detect any contamination. Data were analyzed using the chi-square test or Fisher exact test (categorical data) and Student t-test (continuous data). Results In total, 150 MSCs were collected from 42 endoscopes. Positive MSCs were observed in 4.0% (4/75) of the sprayed group and 1.3% (1/75) of the control group (95% confidence interval, 30.34–0.31; p>0.05), all of which were contributed by colonoscopes. Colonoscope were more prone to positive MSC (mean difference in percentage, p0.05), with environmental and skin flora being the primary contaminants. Conclusions IFS may be applied when delayed endoscope processing is necessary, but with caution when applied to colonoscopes. However, further research is warranted to verify the result.

Abstract The Atlantic Meridional Overturning Circulation (AMOC) is a key player in climate. Here, we employ an ensemble of water hosing experiments to examine mechanisms of AMOC weakening and its subsequent impact on the Labrador Sea open-ocean deep convection. The subpolar AMOC decline in response to the external freshwater flux released over the southern Nordic Sea is dominated by that across the eastern subpolar North Atlantic, and the largest subpolar AMOC decline is at the relatively dense level around $${\sigma }_{0}=27.84\,{{{\rm{kg}}}}\,{{{\rm{m}}}}^{-3}$$ σ 0 = 27.84 kg m − 3 . The AMOC decline is associated with subsurface cooling in the subpolar North Atlantic and the decline in the deep ocean west–east density contrast across the subpolar basin. Contrary to previous studies showing that the AMOC decline is caused by subsurface warming through the shutdown of the Labrador Sea open-ocean deep convection, our results reveal a different response, i.e., a strengthening of the Labrador Sea open-ocean deep convection, which is not a cause of the AMOC decline. The strengthening of the Labrador Sea open-ocean deep convection is mainly due to the relatively stronger freshening in the deep Labrador Sea associated with the freshening/weakening of the Iceland-Scotland Overflow, and thus reduced vertical stratification in the central Labrador Sea.

Abstract Background Tracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants. Methods Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics. The relationship between epidemic trends and control strategies were evaluated. Bayesian phylogeographic reconstruction was employed to estimate and contrast the spatiotemporal dynamics of the Alpha and Delta variants over time. Results Here we reveal that the Alpha variant displays rapid lineage diversification, accompanied by the acquisition of a spike E484K mutation that coincides with the national implementation of mass COVID-19 vaccination. Despite nationwide control strategies and increased vaccination coverage, the Alpha variant was quickly displaced by Delta variants that exhibits a higher effective reproductive number. Phylogeographic inference indicates that the Alpha variant was introduced through south-central region of Cambodia, with strong diffusion rates from the capital of Phnom Penh to other provinces, while the Delta variant likely entered the country via the northern border provinces. Conclusions Continual genomic surveillance and sequencing efforts, in combination with public health strategies, play a vital role in effectively tracking and responding to the emergence, evolution and dissemination of future emerging variants.

Abstract Dysbiosis of the gut-liver axis increases the risk of bacterial and metabolite influx into the liver, which may contribute to the development of hepatocellular carcinoma (HCC). In this study, we compared the microbiomes in HCC tumors and adjacent tissues. We examined the HCC tumors and adjacent tissues from 19 patients diagnosed with HCC. We find that the liver tissues from HCC patients with capsule invasion presented higher alpha diversity at the genus level than those without. The bacterial compositions in liver tissues of HCC patients at stage II differed from those at stage I and Advanced, respectively. Metagenomic profiling revealed that order Actinomycetales was enriched in the HCC patients at advanced stages. Order Lactobacillales, family Veillonellaceae, genera Rhodobacter and Megasphaera are enriched in tumors of HCC patients, whereas genus Pseudochrobactrum is enriched in the adjacent tissues from HCC patients. An increased abundance of class Actinobacteria and order Actinomycetales is observed in the HCC patients with cirrhosis. In contrast, phylum Firmicutes, classes Clostridia and Betaproteobacteria, and order Clostridiales are enriched in those without cirrhosis. The presence of various types of bacterial 16S rRNAs in HCC tumors and adjacent tissues indicates the presence of various bacterial communities therein. Our study provides information about differentially abundant intrahepatic bacteria in patients with HCC. The differences found may support possible diagnostic and personalized therapeutic implications for HCC.

Abstract Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded as a significant role in transcriptional regulation in many tissues. However, the role of histone lactylation in the metabolic center, the hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion of family with sequence similarity 172, member A (Fam172a) can increase histone lactylation and protect mice against diet-induced obesity (DIO) and related metabolic disorders. Conversely, overexpression of Fam172a in POMC neurons led to an obesity-like phenotype. Using RNA-seq and CUT&Tag chromatin profiling analyzes, we find that knockdown of Fam172a activates the glycolytic process and increases peptidylglycine α-amidating monooxygenase (PAM), which affects the synthesis of α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition of lactate production clearly abrogates the anti-obesity effect of PFKO (POMC-Cre, Fam172a loxP/loxP , POMC neurons Fam172a knockout). These findings highlight the importance of Fam172a and lactate in the development of obesity and our results mainly concern male mice.

Abstract The genome is intricately folded into chromatin compartments, topologically associating domains (TADs) and loops unique to each cell type. How this higher-order genome organization regulates cell fate transition remains elusive. Here we show how a single non-neural progenitor transcription factor, PTF1A, reorchestrates the 3D genome during fibroblast transdifferentiation into neural stem cells (NSCs). Multiomics analyses integrating Hi-C data, PTF1A and CTCF DNA-binding profiles, H3K27ac modification, and gene expression, demonstrate that PTF1A binds to subTAD boundaries subsequently associated with elevated CTCF binding and enhanced boundary insulation, and reorganizes chromatin loops, leading to gene expression changes that drive transdifferentiation into NSCs. Moreover, PTF1A activates enhancers and super-enhancers near low-insulation boundaries and modulates H3K27ac deposition, promoting cell fate transitions. Together, our data implicate an involvement of 3D genome in transcriptional and cell fate alterations, and highlight an essential role for PTF1A in gene expression control and multiscale 3D genome remodeling during cell reprogramming.

Most of the existing accurate positioning systems for underground personnel are based on UWB positioning technology and adopt the layout mode of personnel positioning card + positioning substation, which can achieve centimeter-level high-precision positioning without occlusion. When underground personnel travel, it is difficult to achieve accurate positioning of passengers due to the influence of a large range of metal occlusion of mining vehicles and dense factors in the compartment on positioning accuracy. To address the above issues, a method for identifying and locating underground personnel in a vehicle is designed. The status of personnel in a vehicle is recognized through multiple information such as vehicle speed monitoring, positioning card posture, and in-vehicle distance measurement. While the onboard positioning card measures distance with the positioning substation in the tunnel, the information of passengers in a vehicle is transmitted to the positioning substation through message reuse, the positioning substation uploads passenger information to the ground data center through the mine ring network. The test results show that the method has a high accuracy in identifying personnel in a vehicle, and the location information of passengers is synchronized with the vehicle position, which can effectively solve the positioning problem of underground personnel boarding.

Abstract Spinal cord injury (SCI) results in significant neural damage and inhibition of axonal regeneration due to an imbalanced microenvironment. Extensive evidence supports the efficacy of mesenchymal stem cell (MSC) transplantation as a therapeutic approach for SCI. This review aims to present an overview of MSC regulation on the imbalanced microenvironment following SCI, specifically focusing on inflammation, neurotrophy and axonal regeneration. The application, limitations and future prospects of MSC transplantation are discussed as well. Generally, a comprehensive perspective is provided for the clinical translation of MSC transplantation for SCI.

Abstract Four distinct species of human coronaviruses (HCoVs) circulate in humans. Despite the recent attention due to SARS-CoV-2, a comprehensive understanding of the molecular epidemiology and genomic evolution of HCoVs remains unclear. Here, we employed primary differentiated human nasal epithelial cells for the successful isolation and genome sequencing of HCoVs derived from two retrospective cohorts in Singapore and Tanzania. Phylodynamic inference shows that HCoV-229E and HCoV-OC43 were subject to stronger genetic drift and reduced purifying selection from the early 2000s onwards, primarily targeting spike Domain A and B. This resulted in increased lineage diversification, coinciding with a higher effective reproductive number (Re>1.0). However, HCoV-NL63 and HCoV-HKU1 experienced weaker genetic drift and selective pressure with prolonged regional persistence. Our findings suggest that HCoV-229E and HCoV-OC43 viruses are adept at generating new variants and achieving widespread intercontinental dissemination driven by continuous genetic drift, recombination, and complex migration patterns.

Background: Existing methods for MRI brain tumor segmentation often suffer from excessive model parameters and suboptimal performance in delineating tumor boundaries. Methods: For this issue, a lightweight MRI brain tumor segmentation method, enhanced by hierarchical feature fusion (EHFF), is proposed. This method reduces model parameters while improving segmentation performance by integrating hierarchical features. Initially, a fine-grained feature adjustment network is crafted and guided by global contextual information, leading to the establishment of an adaptive feature learning (AFL) module. This module captures the global features of MRI brain tumor images through macro perception and micro focus, adjusting spatial granularity to enhance feature details and reduce computational complexity. Subsequently, a hierarchical feature weighting (HFW) module is constructed. This module extracts multi-scale refined features through multi-level weighting, enhancing the detailed features of spatial positions and alleviating the lack of attention to local position details in macro perception. Finally, a hierarchical feature retention (HFR) module is designed as a supplementary decoder. This module retains, up-samples, and fuses feature maps from each layer, thereby achieving better detail preservation and reconstruction. Results: Experimental results on the BraTS 2021 dataset demonstrate that the proposed method surpasses existing methods. Dice similarity coefficients (DSC) for the three semantic categories ET, TC, and WT are 88.57%, 91.53%, and 93.09%, respectively.

Excessive production and widespread application of antibiotic has led to residues in environmental matrices worldwide. There is limited knowledge of the concentrations of antibiotics bound to ambient fine particulate matter (PM2.5) and their health risks. We investigated the occurrence, sources, environmental driving factors, and health risks of antibiotics in PM2.5 samples collected from Beijing and Shijiazhuang, China, during periods of high air pollution. Using ultra-high performance liquid chromatography-tandem mass spectrometry, 25 antibiotics were detected in PM2.5 at concentrations ranging from undetectable to 774.7 pg/m3. These compounds were predominantly tetracyclines and macrolides. The positive matrix factorization model was used to pinpoint the main sources of these antibiotics as pharmaceutical and medical waste, sewage treatment plants, and livestock emissions, with contributions of 39.1 %, 31.7 %, and 29.2 % respectively, to the total concentrations. Crucial environmental driving factors were determined using a linear mixed-effects model and random forest model. Most antibiotics showed a positive correlation with gaseous pollutants and a negative correlation with meteorological factors. PM2.5, PM10, and CO had the highest influence. The estimated daily intake and hazard quotient (HQ) were calculated to assess the human inhalation exposure risks for these antibiotics, and children aged 0–6 years had the highest intake of 102.8 pg/kg/day. Although the calculated health risk of antibiotic inhalation was low (HQ < 1), considering that exposure to antibiotics via inhalation occurs over long periods and these compounds accumulate, further attention should be given to health risks associated with this exposure. Our results provide valuable insight for environmental planning and policymaking concerning antibiotic pollution and its associated health risks.

Introduction: Chronic heart failure (CHF) is considered to be the last battlefield of cardiovascular disease. Jinxinkang granule (JXK) is an integrated traditional Chinese medicine formula for treating CHF. Our previous clinical study showed that JXK could increase the left ventricular ejection fraction and reduce concomitant symptoms in patients with CHF. However, the molecular mechanism underlying the action of JXK on CHF has yet to be fully illustrated. Methods: Sprague-Dawley (SD) rats under left anterior descending artery ligation model, C57BL/6 mice subcutaneously injected isoproterenol (ISO) model in vivo and H9c2 cells under oxygen glucose deprivation (OGD) in vitro were used to evaluate the effect of JXK against CHF. Cardiac function and morphology assessment using M-mode echocardiography, H&E/Masson/WGA staining, western blotting analysis, real-time PCR detection, ATP and cAMP assays were used to explore the mechanism of JXK against CHF. Results: JXK improved cardiac function and ameliorated cardiac fibrosis in both LAD-induced CHF rats and ISO-induced CHF mice, and protected cardiomyocytes from OGD injury in H9c2 cells. Moreover, JXK increased the level of ATP content and enhanced fatty acid oxidation by increasing CD36, CPT1A and ACADM expression. Mechanism study showed that JXK increased the GPER expression and cAMP level, promoted AMPK phosphorylation and PGC-1α expression. Additionally, molecular docking analysis showed that dihydroisotanshinone I has a high binding affinity with GPER at -8.5 kcal/mol, which has the similar binding sites with G-1, a GPER agonist. Importantly, after using the inhibitor of GPER (G15), the cardioprotective effect of JXK and the enhancing effect on the fatty acid oxidation were blocked. Conclusion: JXK effectively activated GPER/AMPK/PGC-1α signaling pathway to enhance the oxidation of fatty acid, thereby promoting cardiac energy metabolism production to ameliorate CHF.

IntroductionMeningioma is a common tumor of the central nervous system but effective therapies for malignant meningiomas are still lacking. Therefore, the development of novel therapeutic reagents is urgently needed. SYHA1813 is a novel compound and our previous study demonstrated its potent anti-tumor activity on glioblastoma through the inhibition of macrophages and human umbilical vein endothelial cells (HUVECs). However, the precise functional role of SYHA1813 in meningiomas remains unclear.MethodWe aimed to investigate the direct tumor-inhibitory effects of SYHA1813 on meningioma both in vitro and in vivo, and explore its potential molecular mechanisms.ResultsOur results showed that SYHA1813 suppressed the proliferation, colony formation, migration, and invasion of meningioma cells in vitro. Furthermore, we found SYHA1813 induced G2/M cell cycle arrest, apoptosis, and cellular senescence. Mechanistically, RNA-seq revealed that SYHA1813 activated the P53 pathway and impaired DNA repair. In vivo, SYHA1813 effectively inhibited the growth of meningioma xenografts in a mouse model. Additionally, in an ongoing first-inhuman phase I trial, this patient with recurrent meningioma provided preliminary clinical evidence supporting the anti-tumor activity of SYHA1813.DiscussionThis study unveiled a novel antitumor mechanism of SYHA1813, showing its ability to directly target and kill meningioma cells in vitro and in vivo. Our findings highlighted the promising potential of SYHA1813 as a therapeutic agent for treating malignant meningiomas.

PurposeCarbapenem-resistant Klebsiella pneumoniae (CRKP) producing carbapenemases poses a global threat to public health. Antimicrobial agent combinations have been promoted as a potential therapeutic strategy for infections. The most effective antimicrobial combinations against CRKP strains producing different carbapenemases are currently unclear, particularly those producing the KPC variant carbapenemases. This study is aimed to evaluate the effectiveness of various antimicrobial agent combinations against CRKP strains with different carbapenemases.MethodsA checkerboard assay involving 24 antimicrobial agent combinations was conducted on 44 strains of carbapenemase-producing CRKP isolated from patients of which 13 CRKP strains carried single KPC variants. The 24 antimicrobial combinations were based on meropenem, polymyxin, tigecycline, ceftazidime/avibactam, respectively. The fractional inhibitory concentration (FIC) indexes were calculated for each combination of antimicrobial agents.ResultsThe distribution of carbapenemases in 44 CRKP strains was as follows: KPC variants (n = 13, 29.5%), KPC-2 (n = 10, 22.7%), metallo-β-lactamases (n = 9, 20.5%), OXA-48-like (n = 12, 27.3%). In the checkerboard assay, the combination of polymyxin and aztreonam exhibited the highest synergistic effect against CRKP strains, with a rate of 95.5% (42/44). This was followed by polymyxin-meropenem at 88.6% (39/44) and polymyxin-levofloxacin at 68.2% (30/44). Additionally, polymyxin-aztreonam combination and polymyxin-meropenem showed the highest sum of synergistic and additive rates of 100.0% against KPC variant-producing CRKP strains. Notably, ceftazidime/avibactam-based combinations exhibited better synergistic effects on KPC variant-producing CRKP strains compared to other CRKP strains with adjusted p value

Pulmonary fibrosis (PF) is a lethal pathological change of fibrotic interstitial lung diseases (ILDs) with abundant fibroblasts proliferation after severely or continually alveolar epithelial cells (AECs) injury. Barely therapies are helpful for PF. Here we use bleomycin intratracheally injection to model PF with or without human umbilical cord–mesenchymal stem cells (hUC–MSCs) and/or nintedanib intervention. RNA-Seq followed with real-time PCR and western blot were used to find out the specific possible mechanisms of the effects of hUC–MSC and nintedanib on PF. Immunostaining, cell counting kit-8 (CCK-8), and 5-bromo-2′-deoxyuridine (BrdU) incorporation assay were used to detect the cell proliferation in vivo or in vitro separately. We found that hUC–MSCs alone had prophylactic, but not therapeutic effects on bleomycin induced mouse PF. Nevertheless, the combination therapy of hUC–MSCs and low-dose nintedanib significantly improved survival and reversed lung fibrosis in PF model mice. The factors secreted by hUC–MSCs have promotional effects on the proliferation both of fibroblasts and AECs. Nintedanib could hamper the facilitation of fibroblasts caused by hUC–MSCs without influence on AECs proliferation, which might be related with the inhibition on FGFR, PDGFR, and VEGFR activities. Our study indicated that the combination therapy of hUC–MSCs and nintedanib should be a promising strategy for PF.

Abstract In this work, the optical transition of self‐trapped excitons (STEs) and the emergent green emission in β‐Ga2O3 samples with/without Sn impurities at various doping levels have been investigated via temperature‐ and power‐dependent photoluminescence. The ultraviolet (UV) emissions ≈ 3.40 eV unanimously exhibit an excitonic nature related to STEs and typical negative thermal quenching (NTQ) characters. The NTQ activation energy decreases from 103.56 to 42.37 meV with the increased electron concentration from 2.1 × 1016 to 6.7 × 1018 cm−3, indicative of the reduced energy barrier that electrons should overcome to form stable STEs due to the lift‐up of Fermi level. In comparison, the green emissions ≈ 2.35 eV with two quenching channels are observed only in samples with Sn impurities at cryogenic temperatures. One channel is the nsnp‐ns2 transition of Sn2+, the other is donor‐acceptor pair recombination via (2VGa‐Sni)2− complex, which is energetically favorable as evidenced by density functional theory calculations. The semi‐classical quantum theory models fitting proves the transition from green to UV emissions with elevated temperature. The enhanced STEs emission with distinguished NTQ effect strengthens evidence that the stable polarons inherently limit the transport of holes in Ga2O3, and also support the potential of Ga2O3 materials for the development of UV optoelectronics.

Sweetpotato with different flesh colors exhibits significant differences in flavor. Nevertheless, research on the identification of the key aromatic compounds in sweetpotato is scarce. Therefore, 40 primary sweetpotato varieties with different flesh colors were analyzed by HS-SPME/GC–MS to characterize the volatile compounds. A total of 121 volatile compounds were detected, with aldehydes, furans and terpenes being the most abundant components. Additionally, 35 compounds were identified as the key aromatic compounds by OAV > 1, of which 17 were found in all varieties and hence considered as the major components of sweetpotato aroma. Further analysis demonstrated that the yellow-fleshed sweetpotato had the strongest aroma, which was presumed due to the aldehydes like (E,E)-2,4-heptadienal, nonanal, (E,E)-2,4-decadienal,etc. that were produced during the degradation of unsaturated fatty acids. The unique sweety and floral aroma of orange-fleshed sweetpotato might be attributed to apocarotenoid volatiles (trans-beta-ionone, β-ionone, geranylacetone, etc.), the derivates of carotenoids. The purple-fleshed sweetpotato exhibited weak aroma with a significantly high terpenoids concentration. Overall, these findings may be the main reason for the different aromas of different colored sweetpotatoes and provides insights into sweetpotato aroma and a theoretical basis for improving sweetpotato aroma.