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Abstract Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.

Abstract A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0–57.9), and a disease control rate of 95.3% (95% CI 84.2–99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1–15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.

Abstract The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p

Abstract Background Growth rate is a crucial economic trait for farmed animals, but the genetic regulation of this trait is largely unknown in non-model organisms such as shrimp. Results In this study, we performed genome-wide phenotypic quantitative trait loci (QTL) and expression quantitative trait loci (eQTL) mapping analyses to identify genes affecting the growth rate of Pacific white shrimp (Litopenaeus vannamei), which is the most commercially-farmed crustacean worldwide. We used RNA-sequencing of 268 individuals in a mapping population, and subsequently validated our findings through gene silencing and shrimp growth experiments. We constructed a high-density genetic linkage map comprising 5533 markers spanning 44 linkage groups, with a total distance of 6205.75 cM and an average marker interval of 1.12 cM. Our analyses identified 11 QTLs significantly correlated with growth rate, and 117,525 eQTLs. By integrating QTL and eQTL data, we identified a gene (metalloreductase STEAP4) highly associated with shrimp growth rate. RNA interference (RNAi) analysis and growth experiments confirmed that STEAP4 was significantly correlated with growth rate in L. vannamei. Conclusions Our results indicate that the comprehensive analysis of QTL and eQTL can effectively identify genes involved in complex animal traits. This is important for marker-assisted selection (MAS) of animals. Our work contributes to the development of shrimp breeding and available genetic resources.

The combination of high-order modulation formats and linewidth-tolerant carrier phase estimation (CPE) can effectively improve spectrum efficiency and relax the limitation of laser linewidth. This paper presents a simple two-stage CPE algorithm for polarization-multiplexed (PM) 32-quadrature amplitude modulation (32-QAM) coherent optical communication systems. The algorithm uses an enhanced QPSK partitioning algorithm combined with a simplified 4th power CPE method for coarse estimation in the initial stage and maximum likelihood (ML) detection in the subsequent fine stage. The CPE algorithm significantly increases the number of symbols used in the first stage of coarse estimation. This results in a significant increase in the stability and reliability of the phase estimation, and the CPE algorithm significantly reduces the computational complexity. The optimal parameters, phase estimation performance, and system performance of the algorithm were investigated by building a 22 Gbaud PM 32-QAM coherent system simulation platform and a 5 Gbaud PM 32-QAM coherent system experimental platform. The results show that the proposed two-stage CPE algorithm has a stronger linewidth tolerance difference than the conventional QPSK, and the two-stage CPE algorithm with an optimal block length of 105 performs comparable to blind phase search (BPS). The optical signal noise Ratio (OSNR) value is 21.2 dB and the bit error rate (BER) is 1.8 × 10−3 for the optimal block length of 105. The receiving-end DSP unit with a flexible scheme and good communication performance will have potential applications in adaptive elastic optical networks.

This research investigates the dynamics of smoke dispersion in a subway train carriage with multiple lateral openings within a ventilated subway tunnel. Numerous extensive full-scale numerical simulations were conducted to analyze the thermal plume distribution within multiple lateral openings of a train carriage, and the longitudinal and transverse maximum excess ceiling temperature. The results reveal that the heat release rates have a greater impact on the airflow in the carriage than velocities ,even when the longitudinal ventilation velocity reaches 8 m/s or the heat release rate reaches 15 MW. The multiple lateral openings cause significant differences in smoke flow characteristics compared to tunnels with both ends open. Additionally, the transverse maximum ceiling excess temperature inclines towards the lateral opening side due to asymmetrical air entrainment. The analysis of longitudinal maximum ceiling excess temperature identified two regions based on the dimensionless heat release rate, showing a linear increase followed by a constant phase dependent on the heat release rate, with a maximum longitudinal excess gas temperature of 1242 K. Additionally, a relationship between the dimensionless heat release rate and the transverse dimensionless maximum ceiling excess temperature was established. This study can be used as a guide for smoke exhaust mitigation and fire safety measures in the event of subway train carriage fires.

Abstract The effectiveness of poly (ADP-ribose) polymerase inhibitors (PARPi) in creating single-stranded DNA gaps and inducing sensitivity requires the FANCJ DNA helicase. Yet, how FANCJ relates to PARP1 inhibition or trapping, which contribute to PARPi toxicity, remains unclear. Here, we find PARPi effectiveness hinges on S-phase PARP1 activity, which is reduced in FANCJ deficient cells as G-quadruplexes sequester PARP1 and MSH2. Additionally, loss of the FANCJ-MLH1 interaction diminishes PARP1 activity; however, depleting MSH2 reinstates PARPi sensitivity and gaps. Indicating sequestered and trapped PARP1 are distinct, FANCJ loss increases PARPi resistance in cells susceptible to PARP1 trapping. However, with BRCA1 deficiency, the loss of FANCJ mirrors PARP1 loss or inhibition, with the detrimental commonality being loss of S-phase PARP1 activity. These insights underline the crucial role of PARP1 activity during DNA replication in BRCA1 deficient cells and emphasize the importance of understanding drug mechanisms for enhancing therapeutic response.

Abstract Background The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. Methods A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3–5 months. Results The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = − 0.21, − 0.21, − 0.27, − 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later. Conclusion The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.

Abstract The tumor microenvironment is reprogrammed by cancer cells and participates in all stages of tumor progression. Neutral ceramidase is a key regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of neutral ceramidase to the reprogramming of the tumor microenvironment is not well understood. Here, we find that deletion of neutral ceramidase in multiple breast cancer models in female mice accelerates tumor growth. Our result show that Ly6C+CD39+ tumor-infiltrating CD8 T cells are enriched in the tumor microenvironment and display an exhausted phenotype. Deletion of myeloid neutral ceramidase in vivo and in vitro induces exhaustion in tumor-infiltrating Ly6C+CD39+CD8+ T cells. Mechanistically, myeloid neutral ceramidase is required for the generation of lipid droplets and for the induction of lipolysis, which generate fatty acids for fatty-acid oxidation and orchestrate macrophage metabolism. Metabolite ceramide leads to reprogramming of macrophages toward immune suppressive TREM2+ tumor associated macrophages, which promote CD8 T cells exhaustion.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34 C > T (p.R12*) and c.194T > G (p.I65R) in NUDT2. Homozygous variants c.34 C > T (p.R12*) or c.186del (p.A63Qfs*3) in NUDT2 were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in NUDT2 and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of NUDT2-related ID and supported the critical developmental involvement of NUDT2.

ABSTRACT: E2F transcription factor 5 (E2F5) gene is a transcription factor, plays an important role in the development of a variety of cells. E2F5 is expressed in human and mouse adipocytes, but its specific function in adipogenesis is unclear. Krüppel-like factor 7 (KLF7) facilitates proliferation and inhibits differentiation in chicken preadipocytes. Our previous KLF7 chromatin immunoprecipitation-sequencing analysis revealed a KLF7-binding peak in the 3′ flanking region of the E2F5, indicating a regulatory role of KLF7 in this region. In the present study, we investigated E2F5 potential role, the overexpression and knockdown analyses revealed that E2F5 inhibited the differentiation and promoted the proliferation of chicken preadipocytes. Moreover, we identified enhancer activity in the 3′ flanking region (nucleotides +22661/+22900) of E2F5 and found that KLF7 overexpression increased E2F5 expression and luciferase activity in this region. Deleting the putative KLF7-binding site eliminated the promoting effect of KLF7 overexpression on E2F5 expression. Further, E2F5 reversed the KLF7-induced decrease in preadipocyte differentiation and increase in preadipocyte proliferation. Taken together, our findings demonstrate that KLF7 inhibits differentiation and promotes proliferation in preadipocytes by enhancing E2F5 transcription.

ObjectiveThis study aimed to assess the knowledge, attitudes and practices among anemia patients toward disease management.MethodsThis web-based cross-sectional study was conducted between September and December 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine). A self-designed questionnaire was developed to collect demographic information of anemia patients, and assess their knowledge, attitudes and practices (KAP) toward disease management.ResultsA total of 396 valid questionnaires were collected. The mean age of the participants was 57.44 ± 16.80 years, and 52.02% were female. The mean knowledge, attitudes, and practices scores were 11.47 ± 1.73 (possible range: 0–14), 27.32 ± 2.96 (possible range: 7–35), and 40.49 ± 6.06 (possible range: 10–50), respectively. Multivariate analysis showed that bachelor’s degree or above was independently associated with sufficient knowledge (OR = 2.372, 95%CI: 1.160–4.853, p = 0.018). Knowledge (OR = 1.350, 95%CI: 1.166–1.563, p

Objective To evaluate the effectiveness of a system based psychological first aid (PFA) training programme for emergency medical first responders in China.Design Parallel-group, assessor-blinded, cluster randomised controlled trial.Setting 42 clusters of health workers from various health facilities in China.Participants 1399 health workers who provide emergency service for survivors of disasters.Interventions One-day system based PFA training programme (PFA) or training as usual (TAU).Primary and secondary outcome measures The primary outcome was the PFA skills, knowledge and attitude (SKA-PFA) score at 2 months postintervention. Secondary outcomes included post-traumatic growth, self-efficacy and professional quality of life.Results The intervention group (n=690) had significantly higher SKA-PFA scores than the control group (n=709) at 2 months postintervention (adjusted mean difference=4.44; 95% CI 1.17 to 7.52; p=0.007; Cohen’s d=0.35). The intervention group also had higher scores on post-traumatic growth (p=0.113, d=0.24), self-efficacy (p=0.032, d=0.20) and professional quality of life (p=0.281, d=0.04).Conclusions The system based PFA training programme was more effective than the TAU in enhancing the PFA knowledge and skills of the emergency medical first responders and in increasing their competence to provide emergency service for survivors in China.Trial registration number ChiCTR2200060464.

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Abstract Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long‐term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B‐Se) and urine selenium (U‐Se) levels were detected in these areas, measuring 416.977 μg/L and 352.690 μg/L and 104.527 μg/L and 51.820 μg/L, respectively. Additionally, the median blood Cd (B‐Cd) and urine Cd (U‐Cd) levels were markedly elevated at 4.821 μg/L and 3.848 μg/L and at 7.750 μg/L and 7.050 μg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 μmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 μmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.

BackgroundGenome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported.Case presentationIn this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.ConclusionThis case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.

This study investigates the impact of varying distances between vertical walls on the propagation of discrete flames in PMMA (Polymethyl Methacrylate) slabs. The primary objective is to analyze the dynamics of flame spread in confined spaces, with a particular focus on how the spacing between vertical walls and the number of PMMA slabs influence flame characteristics. Experimentally, flame spread rate, mass loss rate, heat release rate, and pyrolysis front dynamics are examined under different confined space distances ranging from 1 to 5 cm using thermally thick PMMA slabs. The findings reveal a significant influence of confined space distance on flame propagation. In narrower spaces (1 to 2 cm), a stack effect leads to a rapid increase in flame height and mass loss rate. As the confined distance increases, this effect gradually diminishes, resulting in a decrease in flame height and mass loss rate. Additionally, the flame spread rate initially rises with increasing confined distance, reaching a peak at 2 cm, before decreasing. Through the application of the law of conservation of energy, the dominant mechanisms of flame spread are deeply analyzed under various confined space conditions. These insights are crucial for understanding and predicting fire spread in confined spaces.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

AbstractHigh translucent zirconia (HTZ) has excellent mechanical properties, biocompatibility, and good semi-translucency making it an ideal material for aesthetic anterior dental implant abutments without antibacterial properties. In the oral environment, the surface of the abutment material is susceptible to microbial adhesion and biofilm formation, which can lead to infection or peri-implantitis and even implant failure. This study aims to promote the formation of a biological seal at the implant-soft tissue interface by modifying the HTZ surface, using the load-bearing capacity of the aluminosilicate porous structure and the broad-spectrum antibacterial effect of silver nanoparticles to prevent peri-implant bacterial infection and inflammation and to improve the success rate and prolong the use of the implant. FE-SEM (field emission scanning electron microscopes), EDS (energy dispersive spectroscopy), and XPS (X-ray photoelectron spectroscopy) results showed that aluminosilicate non-vacuum sintering can form open micro- and nanoporous structures on HTZ surfaces, and that porous aluminosilicate coatings obtain a larger number, smaller size, and more uniformly shaped silver nanoparticles than smooth aluminosilicate coatings, and could be deposited deeper in the coating. The ICP-AES (inductively coupled plasma-atomic emission spectroscopy) results showed that the early silver ion release of both the smooth silver coating and the porous silver coating was obvious, the silver ion concentration released by the former was higher than that of the latter. However, the silver ion concentration released by the porous silver coating was higher than that of the smooth coating when the release slowed down. Both smooth and porous silver coatings both inhibited E. coli (Escherichia coli), S. aureus (Staphylococcus aureus), and L. acidophilus (L. acidophilus), and porous silver coatings had stronger antibacterial properties. The silver coating was successfully constructed on the surface of HTZ, through aluminium silicate sintering and silver nitrate solution impregnation. It was found that the high concentration environment of silver nitrate solution was more advantageous for nano-Ag deposition, and the non-vacuum sintered porous surface was able to obtain a larger number of nano-Ag particles with smaller sizes. The porous Ag coating exhibited superior antibacterial properties. It was suggested that the HTZ with silver coating had clinical application, and good antibacterial properties that can improve the survival rate and service life of implants.

[Introduction] In view of the economic benefits of AGC frequency regulation project of combined energy storage in Guangdong coal-fired power plant, the method of establishing typical engineering cases is demonstrated. [Method] This article summarized the latest version of frequency regulation auxiliary market revenue settlement rules in the southern region and calculated the frequency regulation performance index of typical 2 × 600 MW coal-fired units using lithium iron phosphate battery energy storage in Guangdong Province, then established a revenue model, estimated or assumed the key parameters such as cost, mileage, clearing price, running time, etc. Finally, under the contract energy management mode, it calculated its economy from the perspective of investors and analyzed the changes of financial index under different total investment, operation year and revenue sharing. [Result] The results show that in the measured case, except for the first sharing scheme, the internal rate of return of capital in other scenarios all exceeds 7%. [Conclusion] The frequency regulation project of lithium iron phosphate battery energy storage in Guangdong has a good return on investment within four years. After that, investors can still be attracted to participate in this project with the decrease of total investment and the increase of share.

Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.

Abstract Background In eukaryotic cells, DNA double strand breaks (DSB) are primarily repaired by canonical non-homologous end joining (c-NHEJ), homologous recombination (HR) and alternative NHEJ (alt-NHEJ). Zinc finger and SCAN domain containing 4 (ZSCAN4), sporadically expressed in 1–5% mouse embryonic stem cells (mESCs), is known to regulate genome stability by promoting HR. Results Here we show that ZSCAN4 promotes DNA repair by acting with Poly (ADP-ribose) polymerase 1 (PARP1), which is a key member of the alt-NHEJ pathway. In the presence of PARP1, ZSCAN4-expressing mESCs are associated with lower extent of endogenous or chemical induced DSB comparing to ZSCAN4-negative ones. Reduced DSBs associated with ZSCAN4 are abolished by PARP1 inhibition, achieved either through small molecule inhibitor or gene knockout in mESCs. Furthermore, PARP1 binds directly to ZSCAN4, and the second ⍺-helix and the fourth zinc finger motif of ZSCAN4 are critical for this binding. Conclusions These data reveal that PARP1 and ZSCAN4 have a protein–protein interaction, and shed light on the molecular mechanisms by which ZSCAN4 reduces DSB in mESCs.

Abstract Aims Heart failure (HF) is a prevalent age‐related cardiovascular disease with poor prognosis in the elderly population. This study aimed to establish the causal relationship between ageing and HF by conducting a bidirectional Mendelian randomization (MR) analysis on epigenetic age (a marker of ageing) and HF. Methods and results Genome‐wide association study data for epigenetic age (GrimAge, HorvathAge, HannumAge, and PhenoAge) and HF were collected and assessed for significant genetic variables. A bidirectional MR analysis was carried out using the random‐effects inverse–variance weighted (IVW) method as the primary approach, while other methods (MR–Egger, weighted median, simple mode, and weighted mode) and multiple sensitivity analyses (heterogeneity analysis, leave‐one‐out sensitivity analysis, and horizontal pleiotropy analysis) were employed to evaluate the impact of epigenetic age on HF and vice versa. Bidirectional MR analysis of two samples revealed that the epigenetic PhenoAge clock increased the risk of HF [IVW odds ratio (OR) 1.015, 95% confidence interval (CI) 1.002–1.028, P = 0.028 and weighted median OR 1.020, 95% CI 1.001–1.038, P = 0.039]. Other results were not statistically significant. Conclusions The bidirectional MR analysis demonstrated a causal link between genetically predicted epigenetic age and HF in individuals of European descent. Further research into epigenetic age in other populations and additional genetic information related to HF is warranted.

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS2), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method.Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C).Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Hepatocellular carcinoma (HCC) stands as the prevailing manifestation of primary liver cancer and continues to pose a formidable challenge to human well-being and longevity, owing to its elevated incidence and mortality rates. Nevertheless, the quest for reliable predictive biomarkers for HCC remains ongoing. Recent research has demonstrated a close correlation between ferroptosis and disulfidptosis, two cellular processes, and cancer prognosis, suggesting their potential as predictive factors for HCC. In this study, we employed a combination of bioinformatics algorithms and machine learning techniques, leveraging RNA sequencing data, mutation profiles, and clinical data from HCC samples in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) databases, to develop a risk prognosis model based on genes associated with ferroptosis and disulfidptosis. We conducted an unsupervised clustering analysis, calculating a risk score (RS) to predict the prognosis of HCC using these genes. Clustering analysis revealed two distinct HCC clusters, each characterized by significantly different prognostic and immune features. The median RS stratified HCC samples in the TCGA, GEO, and ICGC cohorts into high-and low-risk groups. Importantly, RS emerged as an independent prognostic factor in all three cohorts, with the high-risk group demonstrating poorer prognosis and a more active immunosuppressive microenvironment. Additionally, the high-risk group exhibited higher expression levels of tumor mutation burden (TMB), immune checkpoints (ICs), and human leukocyte antigen (HLA), suggesting a heightened responsiveness to immunotherapy. A cancer stem cell infiltration analysis revealed a higher similarity between tumor cells and stem cells in the high-risk group. Furthermore, drug sensitivity analysis highlighted significant differences in response to antitumor drugs between the two risk groups. In summary, our risk prognostic model, constructed based on ferroptosis-related genes associated with disulfidptosis, effectively predicts HCC prognosis. These findings hold potential implications for patient stratification and clinical decision-making, offering valuable theoretical insights in this field.

In this paper, the effects of varying material widths on the propagation of discrete fires within diverse confined space conditions are investigated experimentally. The width-induced mechanisms influencing the flame spread of discrete solid surfaces in distinct confined spaces are comprehensively discussed, encompassing flame characteristics, pyrolysis front dynamics, flame spread rate, and mass loss rate. The findings reveal that the dimensionless flame height and width conform to a negative power relationship at varying restricted distances. Furthermore, a positive correlation between the width of the PMMA in confined spaces and both the flame spread rate and the mass loss rate is established. Notably, when the width is fixed, the confined space plays a dominant role in the propagation of flames. As the restricted distance decreases, the flames become more slender. Additionally, flame height, flame spread rate, and mass loss rate increase with the widening of the material. However, as the restricted distance becomes smaller, the effect of width becomes less pronounced. Under conditions of same restricted distance, an increased width results in a higher radiation factor, thereby enhancing the thermal feedback of the wall to the material, which in turn accelerates the spread rate of discrete flames. Moreover, due to the dominant role of radiant heat feedback provided by the confined walls to the discrete PMMA panels, the proportion of heat transferred by convection in the flames is minimal. Consequently, the influence of the convective coefficient's width variation on flame spread is relatively minor within confined spaces. Ultimately, an energy conservation model under confined spaces was established, which facilitated the analysis of the comprehensive mechanism of flame spread influenced by varying confined spaces and material widths.

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.

Introduction: Orangutans, classified under the Pongo genus, are an endangered non-human primate (NHP) species. Derivation of induced pluripotent stem cells (iPSCs) represents a promising avenue for conserving the genetic resources of these animals. Earlier studies focused on deriving orangutan iPSCs (o-iPSCs) from Sumatran orangutans (Pongo abelii). To date, no reports specifically target the other Critically Endangered species in the Pongo genus, the Bornean orangutans (Pongo pygmaeus).Methods: Using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells to generate iPSCs (bo-iPSCs) from a female captive Bornean orangutan. In this study, we evaluate the colony morphology, pluripotent markers, X chromosome activation status, and transcriptomic profile of the bo-iPSCs to demonstrate the pluripotency of iPSCs from Bornean orangutans.Results: The bo-iPSCs were successfully derived from Bornean orangutans, using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells. When a modified 4i/L/A (m4i/L/A) culture system was applied to activate the WNT signaling pathway in these bo-iPSCs, the derived cells (m-bo-iPSCs) manifested characteristics akin to human naive pluripotent stem cells, including high expression levels of KLF17, DNMT3L, and DPPA3/5, as well as the X chromosome reactivation. Comparative RNA-seq analysis positioned the m-bo-iPSCs between human naive and formative pluripotent states. Furthermore, the m-bo-iPSCs express differentiation capacity into all three germlines, evidenced by controlled in vitro embryoid body formation assay.Discussion: Our work establishes a novel approach to preserve the genetic diversity of endangered Bornean orangutans while offering insights into primate stem cell pluripotency. In the future, derivation of the primordial germ cell-like cells (PGCLCs) from m-bo-iPSCs is needed to demonstrate the further specific application in species preservation and broaden the knowledge of primordial germ cell specification across species.

Abstract Tumor-associated high endothelial venules (TA-HEVs) mediate lymphocyte entry into tumors. Therefore, combined anti-angiogenesis therapy and programmed death-1 (PD-1) inhibitors might stimulate tumor immunity. This study will explore the TA-HEVs and real-world data of the combination therapy in non-small cell lung cancer (NSCLC). Firstly, we found a certain relationship between HEVs and immune effector cells by multiple immunofluorescence staining. We then analyzed the efficacy of immunotherapy combined with anti-angiogenesis therapy in advanced NSCLC patients by collecting real-world clinical data. Finally, we explored the predictive value of HEVs in combination therapy by analyzing pre-treatment pathological slides of patients with multiple immunofluorescence and RNA sequencing. Immunofluorescence staining of high endothelial venules (PNAd+) reveals that the frequency of HEVs is positively correlated with tumor-infiltrating stem-like CD8+ T cells (TCF-1+PD-1+) in the TME of advanced NSCLC patients (P = 0.0221). We retrospectively analyzed the efficacy of 96 patients with advanced NSCLC who received PD-1 inhibitors combined with anti-angiogenesis therapy in the real-world. The median PFS of patients combined with anti-angiogenesis therapy was longer than that of patients without anti-angiogenesis therapy (9.7 vs 8.6 months, P = 0.041). Multiple immunofluorescence staining of tumor biopsies before treatment from 14 patients with advanced NSCLC reveals that PNAd+ is predictive of better response and survival upon PD-1 inhibitors combined with anti-angiogenesis therapy (P = 0.0274). In addition, we collected peripheral blood from an effective group of patients for RNA sequencing and found that immune cells activation-related gene expression scores were higher. Combined anti-angiogenic and anti-PD-1 therapy stimulates tumor immunity through TA-HEVs formation. TA-HEVs not only mediate immune cell entry into tumors, but also are associated with the efficacy of PD-1 inhibitors and anti-angiogenesis therapy in NSCLC.

Abstract Background The identifying of B-cell lymphoma 2 (Bcl-2) as a therapeutic target has led to a paradigm shift in acute myeloid leukemia (AML) treatment. Pyroptosis is a novel antitumor therapeutic mechanism due to its cytotoxic and immunogenic effects. The combination of venetoclax and hypomethylating agents (HMAs) has been shown to lead to durable responses and significantly improve prognosis in patients with AML. However, our understanding of the mechanisms underlying this combinatorial activity is evolving. Methods We investigated whether the Bcl-2 inhibitor venetoclax induces AML cell pyroptosis and identified pyroptosis effector proteins. Via using western blotting, immunoprecipitation, RNA interference, CCK8 assays, and LDH assays, we explored the mechanism underlying the pyroptotic effect. The relationship between the expression of the pyroptosis effector protein GSDME and AML prognosis was investigated. The effect of GSDME demethylation combined with venetoclax treatment on pyroptosis was investigated and confirmed in mouse models and clinical samples. Results Venetoclax induces pyroptosis that is mediated by caspase-3-dependent GSDME cleavage. Mechanistically, venetoclax upregulates caspase-3 and GSDME cleavage by activating the intrinsic apoptotic pathway. GSDME is downregulated in AML by promoter methylation, and low GSDME expression is significantly associated with poor prognosis, based on public databases and patient sample analysis. In vivo and in vitro experiments showed that GSDME overexpression or HMAs-mediated restoration of GSDME expression significantly increased venetoclax-induced pyroptosis in AML. Conclusion GSDME-mediated pyroptosis may be a novel aspect of the antileukemic effect of Bcl-2 inhibitors. This finding offers new insights into potential biomarkers and therapeutic strategies, identifying an important mechanism explaining the clinical activity of venetoclax and HMAs in AML.

ABSTRACTHigh Spatial and Spectral Resolution (HSSR) remote-sensing images can provide rich spectral bands and detailed ground information, but there is a relative lack of research on this new type of remote-sensing data. Although there are already some HSSR datasets for deep learning model training and testing, the data volume of these datasets is small, resulting in low classification accuracy and weak generalization ability of the trained models. In this paper, an HSSR dataset Luojia-HSSR is constructed based on aerial hyperspectral imagery of southern Shenyang City of Liaoning Province in China. To our knowledge, it is the largest HSSR dataset to date, with 6438 pairs of 256 × 256 sized samples (including 3480 pairs in the training set, 2209 pairs in the test set, and 749 pairs in the validation set), covering area of 161 km2 with spatial resolution 0.75 m, 249 Visible and Near-Infrared (VNIR) spectral bands, and corresponding to 23 classes of field-validated ground coverage. It is an ideal experimental data for spatial-spectral feature extraction. Furthermore, a new deep learning model 3D-HRNet for interpreting HSSR images is proposed. The conv-neck in HRNet is modified to better mine the spatial information of the images. Then, a 3D convolution module with attention mechanism is designed to capture the global-local fine spectral information simultaneously. Subsequently, the 3D convolution is inserted into the HRNet to optimize the performance. The experiments show that the 3D-HRNet model has good interpreting ability for the Luojia-HSSR dataset with the Frequency Weighted Intersection over Union（FWIoU） reaching 80.54%, indicating that the Luojia-HSSR dataset constructed in this paper and the proposed 3D-HRnet model have good applicable prospects for processing HSSR remote sensing images.

Abstract Lung squamous cell carcinoma (LUSC) is associated with a worse prognosis than other histological subtypes of non-small cell lung cancer. Due to the vital role of CD8+ T cells in anti-tumor immunity, the characterization of CD8+ T cell infiltration-related (CTLIR) gene signature in LUSC is worthy of in-depth exploration. In our study, tumor tissues of LUSC patients from Renmin Hospital of Wuhan University were stained by multiplex immunohistochemistry to evaluate the density of infiltrated CD8+ T cells and explore the correlation with immunotherapy response. We found that the proportion of LUSC patients who responded to immunotherapy was higher in the high density of CD8+ T cell infiltration group than in the low density of CD8+ T cell infiltration group. Subsequently, we collected bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) database. The abundance of infiltrating immune cells in LUSC patients was analyzed by using CIBERSORT algorithm, and weighted correlation network analysis was performed to identify the co-expressed gene modules related to CD8+ T cells. We then developed a prognostic gene signature based on CD8+ T cell co-expressed genes and calculated the CTLIR risk score, which stratified LUSC patients into high-risk and low-risk groups. With univariate and multivariate analyses, the gene signature was identified as an independent prognostic factor in LUSC patients. The overall survival of LUSC patients in the high-risk group was significantly shorter than that of the low-risk group in the TCGA cohort, which was validated in Gene Expression Omnibus datasets. We analyzed immune cell infiltration in the tumor microenviroment and found fewer CD8+ T cells and more regulatory T cell infiltration in the high-risk group, which is characterized as an immunosuppressive phenotype. Furthermore, the LUSC patients in the high-risk group were predicted to have a better response to immunotherapy than those in the low-risk group when treated with PD-1 and CTLA4 inhibitors. In conclusion, we performed a comprehensive molecular analysis of the CTLIR gene signature in LUSC and constructed a risk model for LUSC patients to predict prognosis and immunotherapy response.

To characterize the structure and dynamics of metal–-organic frameworks (MOFs) in-depth at the molecular level, it is necessary to pursue high-resolution solid-state magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. Spectral resolution is usually affected by the quality of materials and various experimental conditions, of which magic angle (MA) accuracy is a crucial determinant. The current industrial criteria for MA calibration based on the common standard of KBr were found insufficient in guaranteeing optimal resolution MAS NMR for highly ordered MOFs. To drive towards higher-resolution MAS NMR spectroscopy, we propose a calibration protocol for more accurate MA with a higher-precision criterion based on 79Br MAS NMR of KBr, where the linewidth ratio of the fifth-order spinning sideband to the central band of KBr should be less than 1.00. As a result, ultrahigh-resolution 13C cross-polarization (CP) MAS NMR of MOF-5 is achieved with minimal linewidths as low as 4 Hz, and therefore MOF-5 can be used as a new standard convenient for verifying MA accuracy and also optimizing 13C CP conditions. Maintaining high-precision MA under variable temperature (VT) was found challenging on certain commercial MAS NMR probes, as was systematically investigated by VT NMR using KBr and MOF-5. Nevertheless, ultrahigh-resolution MAS NMR spectroscopy with stable MA under VT is employed to reveal fine structures and linker dynamics of a series of Zn-based MOFs with highly regulated structures. The ultrahigh-resolution NMR methodcan be generally applied to study a broad range of MOFs and other materials.

The Pacific white shrimp (Litopenaeus vannamei) is the most commercially-farmed shrimp species globally and is of significant ecological and economic importance. Here we report a high-quality genome assembly of L. vannamei using PacBio reads and Hi-C data. The assembly spans 1.87 Gb with scaffold N50 of 39.7 Mb and 87% of estimated genome size is assigned to 44 pseudochromosomes. The genome contains 24,861 protein-coding genes and a high proportion of transposable elements (64.33%). Significant expansion of gene families was observed in the genome related to locomotion, vision, and neural transmission, including via expansion of actin, myosin, rhodopsin, and neurotransmitter-gated ion-channel ligand binding domain genes, potentially revealing mechanisms underlying their evolved benthic adaptations. The genome assembly of L. vannamei provides valuable resources for future genetic research, breeding, and improvement of aquaculture traits, and will facilitate the research of genetic changes during evolution.

Understanding the characteristics of smoke layer thickness is vital for accurate fire detection, efficient smoke exhaust and safe evacuation in tunnel fire. Nevertheless, smoke flow in tunnels with arched ceiling may show different characteristics from the tunnels with flat roof which is usually studied. Theoretical analysis was conducted on the smoke flow characteristics and thickness under the curved roof of natural ventilation tunnel, and further, numerical simulations were performed to elucidate and verify the mechanism. The results show that smoke mass flow rate is positively correlated with heat release rate(HRR) and section radius. However, the smoke layer thickness is not significantly affected by HRR, and is positively related to the section radius. Based on the mass conservation, a practical prediction model for smoke layer thickness under arched ceiling was derived, and an empirical equation for estimating the total smoke mass flow rate was also proposed. The results presented fairly good agreement with simulations and experimental data from previous works.

Perylene diimides (PDIs) with high fluorescence quantum yield and well π-conjugated plane have been widely studied to construct supramolecular aggregates via noncovalent interactions and to further develop supramolecular fluorescent sensors triggered by analytes. This review summarizes recent progress in the design strategies and sensing applications of the PDI supramolecular aggregates. Besides the inherent π-π stacking of the PDI plane, the additional driving forces to promote the construction of PDI supramolecular aggregates are classified into four parts including hydrogen bonding interactions, electrostatic interactions, metal-coordination interactions and host-guest interactions. Then, the PDI supramolecular aggregates can be used to detect metal ions, biomolecules and organic molecules. Finally, the potential future developments of the PDI supramolecular aggregates in sensing applications are discussed.

This experimental study delves into the fire characteristics within a long and narrow compartment equipped with multiple lateral openings. The investigation encompasses aspects such as radiant heat flow, temperature distribution, and smoke layer height. The presence of lateral openings introduces asymmetry in suction, resulting in augmented radiative heat flow on the rear side of the fire source compared to the front and left sides. Smoke stratification remains stable, with minimal temperature influence from the fire source power at one opening and negligible impact at the other. Employing a customized two-dimensional method for thermal estimation, our experimental data display lower results than previous predictions due to structural disparities. The utilization of the N-percentage rule unveils two discernible regions in smoke layer height behavior: stable and decreasing, a pattern consistent across varying heat release rates. These insights offer valuable predictive tools for discerning fire characteristics in elongated, restricted compartments with multiple lateral openings. Consequently, this study enhances comprehension and informs safety measures within such configurations, contributing to the broader field of fire safety engineering.

In this paper, we investigate simultaneously transmitting and reflecting reconfigurable intelligent surfaces (STAR-RIS), which enables to communicate with users in both sides by transmitting signals to users forward and reflecting signals to users backward simultaneously. We consider a communication system with a STAR-RIS, a base station (BS) and many users to maximize the minimum user energy efficiency (EE) by jointly optimizing active beamforming, transmission and reflection coefficients with power constraint. Considering the fractional programming form of the formulated problem, we adopt Dinkelbach algorithm to transform the problem into the form of convex function subtraction, and then divide it into two sub-problems optimizing the beamforming vectors at BS and coefficient matrices at STAR-RIS separately. With the two subproblems fixed, an Alternating Optimization (AO) algorithm is proposed to solve the maximize minimum user EE fair optimization problem. Numerical results demonstrate that STAR-RIS can enhance energy and spectrum efficiency of the STAR-RIS communication system, and the proposed algorithm maximizes the minimum EE effectively to ensure user fairness.

The Three-River Headstreams Region (TRHR) serves as the cradle of China’s three major rivers—the Yangtze, Yellow, and Lancang—rendering its water conservation (WC) capacity quintessentially significant for Asian water resource security. This study integrated the InVEST model and random forest model to holistically elucidate the spatiotemporal characteristics and factors influencing WC in the TRHR from 1980 to 2018. The results revealed that the WC growth rate was 5.65 mm/10a in the TRHR during the study period, yet pronounced regional disparities were observed among different basins, especially with the Lancang River Basin (LRB), which exhibited a decrease at a rate of 5.08 mm per decade despite having the highest WC. Through Theil–Sen trend analysis, the Mann–Kendall abrupt change test, and the cumulative deviation method, meteorological, vegetative, and land use abrupt changes in approximately 2000 were identified as the primary drivers for the abrupt surge in WC within the TRHR. Furthermore, precipitation and the aridity index were the core feature variables affecting WC. However, a positive transition in land use patterns post-2000 was also revealed, and its favorable effect on WC was not as significant as the abrupt climatic changes. This study offers new perspectives on managing multidimensional spatiotemporal data and contributes to laying the groundwork for machine learning applications in water conservation. Additionally, it potentially provides useful references for decision-making processes related to ecosystem security.

5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia, and cranial nerves involvement. Here, we report three new cases with MTHFS deficiency from two non-consanguineous Chinese families. All patients showed white matter dysplasia and global developmental delay, of which only patient 1 and 2 manifested tonic-clonic seizures. Moreover, patient 2 had severe eczema and patient 3 had recurrent diarrhea. Both phenotypic features are firstly found in MTHFS deficiency. Trio whole-exome sequencing and sanger sequencing were used to identify four novel variants, p.Y169Tfs*17, p.S53F, c.117+1delG, and p.E61G in the MTHFS gene. The identification of four novel pathogenic variants and varied clinical features in three affected patients expands the genotype and phenotype spectrum of MTHFS deficiency. We also reviewed all cases of MTHFS deficiency that had previously been reported. The experience of diagnosis and treatment from these cases provides us a more comprehensive understanding of this rare disease.

A series of experiments were carried out within a scaled-down, elongated, and narrow space featuring multiple lateral doors. These experiments aimed to thoroughly examine the fire characteristics both inside the enclosed compartment and within the connected tunnel, which were induced by the fire occurring in the compartment. It shows that the classic maximum temperature model obtained from a single confined space underestimates or overestimates the values in the carriage and tunnel, and the three-region plume law cannot effectively cover the temperature values inside the carriage, the prediction relations for the double confined space scenario are proposed. The rate of temperature decrease beneath the ceiling in the double long-narrow confined space is greater than in a single confined space, with a significantly reduced impact of HRR on the decay rate. The study also provides a segmented characterization of the influence of HRR on temperature attenuation. Additionally, distinct flame extension and spillover patterns are observed at different fire source locations. These include ceiling jet flame overflow primarily from the upper part of the lateral door and direct overflow from the entire door height. The study's findings offer valuable insights for fire assessment and control in complex confined rail systems.

As an important forest firefighting equipment in China, the 6 MF-30 pneumatic fire extinguisher has the problem of engine overheat resulting in rotational speed reduction during application. Adding water as a medium to form an airflow-water synergistic jet can improve the fire extinguishing effect. In this paper, through experiments, flow field analysis was carried out on the wood crib fire extinguishing scene and fire extinguishing effects were analyzed. It was found that the extinguisher with a rotational speed below a certain degree could not extinguish the wood crib fire. The airflow-water synergistic jet can effectively improve the fire extinguishing efficiency, greatly reduce the fire extinguishing time, and reduce the risk of reignition. The best effect is to use 4 nozzles to inject water into the outlet of the air duct, which can achieve the effect of direct injection with water pipe in the case of limited water source.

ObjectiveTo prospectively assess whether air pollution, including PM2.5, PM10, and NOx, is associated with the risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia, and to investigate the potential relationship between air pollution and genetic susceptibility in the development of AD.Methods and resultsOur study included 437,932 participants from the UK Biobank with a median follow-up period of over 10 years. Using a Cox proportional hazards model, we found that participants exposed to PM2.5 levels of ≥10 μg/m3 had a higher risk of developing all-cause dementia (HR = 1.1; 95% CI: 1.05–1.28; p

The fire-extinguishing capability of the overheating 6 MF-30 pneumatic fire extinguisher needs to be improved. To enhance its fire-extinguishing capability, this study proposes a method of adding water through nozzles. The study conducted flow-field simulations to determine the appropriate nozzle position and replicate the synergistic jet effects using varying number of nozzles. Experimental studies were carried out to validate the simulation and demonstrate the efficiency of the synergistic jet in extinguishing fires directly. The findings show that placing the nozzle at the air duct outlet and using a higher number of nozzles is more efficient. Additionally, the synergistic jet has a better fire-extinguishing performance than pure airflow because of the cooling effects resulting from the water mist and collaborative action observed during the experimental studies. This research has significant implications for improving the efficiency and effectiveness of pneumatic fire extinguishers while advancing fire-extinguishing technology and firefighting technology.

Abstract Background The association between body mass index (BMI) and Alzheimer's disease (AD) remains controversial. Genetic and environmental factors are now considered contributors to AD risk. However, little is known about the potential interaction between genetic risk and BMI on AD risk. Objective To study the causal relationship between BMI and AD, and the potential interaction between AD genetic risk and BMI on AD risk. Methods and Results Using the UK Biobank database, 475,813 participants were selected for an average follow-up time of more than 10 years. Main findings: 1) there was a nonlinear relationship between BMI and AD risk in participants aged 60 years or older (p for non-linear 30 kg/m2) group was associated with a lower AD risk (HR = 0.741; 95% CI 0.618–0.888, p

Abstract Dilated cardiomyopathy (DCM) is a condition of impaired ventricular remodeling and systolic diastole that is often complicated by arrhythmias and heart failure with a poor prognosis. This study attempted to identify autophagy-related genes (ARGs) with diagnostic biomarkers of DCM using machine learning and bioinformatics approaches. Differential analysis of whole gene microarray data of DCM from the Gene Expression Omnibus (GEO) database was performed using the NetworkAnalyst 3.0 platform. Differentially expressed genes (DEGs) matching (|log2FoldChange ≥ 0.8, p value

COVID-19 is a constantly challenging global health issue due to its strong intensity, rapid mutation and high infectiousness. The new Delta and Omicron variants have triggered massive outbreaks worldwide. Even China, which has done a good job in outbreak prevention, is still heavily affected by the virus. The long-term fight against multiple COVID-19 outbreaks is ongoing. In this study, we propose an SEIQR model that considers the incubation period and quarantine measurement. We verified our model using actual outbreak data from four Chinese cities. Numerical simulations show that a five-day delay results in a double resurgence scale. Our model can be used as a tool to understand the spread of the virus quantitatively and provide a reference for policymaking accordingly.

We aimed to evaluate the cerebroprotective eff ects of Yizhitongmai Granule and its decomposed recipes on vascular dementia (VD) rats via the Nod-like receptor protein 3 (NLRP3) infl ammasome pathway. Sixty rats were randomly divided into Sham, VD Model, Yizhitongmai Recipe, Bushen Recipe, Tongluo Recipe and positive control groups (n=10). From 12 d aft er operation, Yizhitongmai Recipe, Bushen Recipe and Tongluo Recipe groups were gavaged with corresponding drug liquid. Th e drugs were administered at 2 mL once a day for 28 consecutive days. Th e reactive oxygen species (ROS), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and lactate dehydrogenase (LDH) in hippocampal tissues were detected using biochemical methods. Tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18) and IL-1β were detected by enzyme-linked immunosorbent assay. Western blotting was performed to detect the expression levels of neuronal growth-associated protein-43 (GAP43), synaptophysin (SYN), aquaporin 4 (AQP4), NLRP3 and Caspase-1. Compared with the Model group, the number of apoptotic cells, levels of ROS, LDH, TNF-α, IL-18, IL-1β, NLRP3 and Caspase-1 decreased, and the levels of SOD, T-AOC, GAP43, SYN and AQP4 increased in the Yizhitongmai Recipe, Bushen Recipe and Tongluo Recipe groups (P0.05). Compared with the Bushen Recipe and Tongluo Recipe groups, the Yizhitongmai Recipe group had fewer apoptotic cells, decreased levels of ROS, LDH, TNF-α, IL-18, IL-1β, NLRP3 and Caspase-1, and increased levels of SOD, T-AOC, GAP43, SYN and AQP4 (P