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Research examining students' socioeconomic outcomes after attaining a bachelor's degree tends to use single measures such as income or occupation (Thomas & Zhang, 2005; Torche, 2015). Yet, socioeconomic status is more complex than single measures. To capture that complexity, this study draws data from the National Center for Education Statistics Baccalaureate and Beyond Longitudinal Study (B&B:08/12) to examine a multidimensional measure of socioeconomic status one and four years after graduation with a bachelor's degree. The findings suggest that college graduates are not guaranteed benefits or low levels of time unemployed. The differences found across groups and time points highlight the importance of considering both monetary and non- monetary aspects of socioeconomic status related to higher education attendance and student success. This study contributes to exploring multidimensional measures to advance the understanding of students' postgraduation outcomes and the continued impact of higher education on students' outcomes beyond completion.

Background: The potential for broadening participation in engineering among Black undergraduates via transfer pathways is considerable, given their large share of the community college population. By understanding the opportunities and challenges presented within the context of transfer, this potential can be realized. Purpose/hypothesis: The goal of this study is to explore ways in which Black students who transitioned from a community college to a 4-year engineering program describe the institutional factors affecting their transfer processes. Design/method: Drawing from a 3-year qualitative research study involving approximately 27 Black engineering transfer students at a large, predominantly White, institution, we present data derived through interviews and focus groups with these undergraduates. Results: Participants expressed that they benefited from supportive institutional agents who offered engineering transfer-related resources. These included both faculty and advisors in their mostly Minority Serving Community Colleges (MSCCs) as well as advisors from the engineering college at the 4-year institution. In addition, respondents described being part of a number of community college programs, including some for Black collegians, that offered resources for transfer. Nonetheless, some participants shared problems that emerged during the transfer process, including having to self-navigate confusing transfer websites or self-advocate to resolve erroneous admissions decisions. Conclusions: We suggest a need to elevate MSCCs as learning environments that can produce future Black engineers. We also recommend a systems-level approach that brings together community colleges and 4-year institutions while also accounting for issues related to resources as well as power dynamics that students may encounter.

Purpose – The modernization of China’s economy is an integral part of Chinese-style modernization. According to the principle of unifying theoretical, historical and practical logic, theoretically explaining the modernization of China’s economy is both a political necessity and a higher scientific requirement. Design/methodology/approach – Following this evolutionary line – from modes of production to the general economic development mechanism and then to patterns of economic operation and development – this paper employs the principal contradiction analysis method to offer an interpretation of China’s economic modernization from the broad Marxist political economy perspective. Findings – In economic terms, “get organized” primarily refers to the development and mutual promotion of team-based and market-based division of labor organizations, as discussed by Karl Marx. “Get organized” (specifically the development of team-based division of labor organizations) acts as the engine of China’s economic modernization and serves as the historical logical starting point. Division of labor is the theoretical logical starting point for interpreting China’s economic modernization. The two of them are congruent, achieving the unity of theoretical and historical logic at the starting point. The development and mutual promotion of these “two types of division of labor” inherently generate the general mechanism of economic development first comprehensively discussed by Marx and Friedrich Engels, which involves the division of labor development and market expansion accumulating cyclically and reinforcing each other. This mechanism drives both the high-speed and high-quality development of China’s economic modernization. Originality/value – The broad Marxist political economy paradigm facilitates explaining China’s economic modernization theoretically, historically and practically with unified logic. “Get organized” serves as both the engine and the realization mechanism of this modernization, with the Communist Party of China (CPC) consistently being the core force of this organizational effort.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Background Passive smoke has a significant impact on lung function and constitutes a critical public health issue, as smoking generates free radicals that damage the lungs and other tissues. Currently, limited research exists on whether the antioxidant melatonin can mitigate lung damage caused by smoking. This study aims to investigate the mechanisms through which melatonin alleviates acute lung disease induced by passive smoking. Methods Rats were divided into five groups (n = 6): a control group and three groups exposed to low, medium, and high concentrations of smoke, and a melatonin treatment group. Results Data indicated that in the high concentration passive smoking group, the alveolar structure of the lung tissue was destroyed, and the total antioxidant capacity in lung tissue diminished as the concentration of smoke increased. The expressions of TNF-α, IL-6, and IL-1β exhibited similar results. The anti-apoptotic factors Bcl-2 and Bcl-xL mRNA level significantly decreased in the high concentration smoking group, while no significant changes were observed in the medium and low concentration groups. Conversely, the high concentration passive smoking increased the pro-apoptotic factors Bax and Caspase-3 mRNA levels. Additionally, endogenous melatonin levels in lung tissue gradually decreased following exposure to smoke, whereas the exogenous melatonin alleviated the changes in inflammatory factors and apoptosis-related factors in lung tissue. Furthermore, at high smoking concentrations, the mRNA levels of lung cancer-related genes vascular endothelial growth factor (VEGF), cytochromeP450 1A1 (CYP1A1), and cytochrome P450 1B1 (CYP1B1 ) were significantly increased, while exogenous melatonin reduced the expression of these genes in lung tissue. Conclusions These findings suggest that melatonin can diminish lung tissue damage, apoptosis, and inflammatory responses induced by passive smoking, as well as decrease the expression of lung cancer-related genes. Further experimental investigations involving exogenous melatonin treatments will be needed.

Objectives: To develop computed tomography (CT)-based models to increase the prediction accuracy of spread through air spaces (STAS) in clinical-stage T1N0 lung adenocarcinoma. Methods: Three cohorts of patients with stage T1N0 lung adenocarcinoma (n = 1258) were analyzed retrospectively. Two models using radiomics and deep neural networks (DNNs) were established to predict the lung adenocarcinoma STAS status. For the radiomic models, features were extracted using PyRadiomics, and 10 features with nonzero coefficients were selected using least absolute shrinkage and selection operator regression to construct the models. For the DNN models, a 2-stage (supervised contrastive learning and fine-tuning) deep-learning model, MultiCL, was constructed using CT images and the STAS status as training data. The area under the curve (AUC) was used to verify the predictive ability of both model types for the STAS status. Results: Among the radiomic models, the linear discriminant analysis model exhibited the best performance, with AUC values of 0.8944 (95% confidence interval [CI], 0.8241-0.9502) and 0.7796 (95% CI, 0.7089-0.8448) for predicting the STAS status on the test and external validation cohorts, respectively. Among the DNN models, MultiCL exhibited the best performance, with AUC values of 0.8434 (95% CI, 0.7580-0.9154) for the test cohort and 0.7686 (95% CI, 0.6991-0.8316) for the external validation cohort. Conclusions: CT-based imaging models (radiomics and DNNs) can accurately identify the STAS status of clinical-stage T1N0 lung adenocarcinoma, potentially guiding surgical decision making and improving patient outcomes.

Objective: To investigate the effects and mechanisms of Xuebijing injection (XBJ) on Chimeric antigen receptor-T (CAR-T) cell function and its therapeutic potential against CAR-T therapy-associated cytokine storms (CRS). Methods: Anti-CD19 CAR-T cells were established based on FMC63 antibodies. Different doses of XBJ (1 and 10 mg/mL) were added to the culture system. Untreated anti-CD19 CAR-T cells served as negative controls. After 48-h co-culture, the effects of XBJ on CAR-T cell function were assessed. Carboxyfluorescein diacetate succinimidyl ester staining was used to assess the effect of XBJ on CAR-T cell proliferation. Flow cytometry, luciferase reporter gene assays, and real time cellular analysis were employed to evaluate the effects of XBJ on CAR-T cell cytotoxicity in vitro. RNA-sequencing was performed to analyze the effects of XBJ on CAR-T cell gene expression. Network pharmacology predicted potential XBJ therapeutic targets for CRS, which were verified in a THP-1 macrophage inflammation model. Results: XBJ enhanced both the proliferation and tumor killing capacities of CAR-T cells. Transcriptome analysis showed that XBJ treatment affects multiple genes and pathways in CAR-T cells, with differential gene enrichment in multiple cell proliferation and growth factor pathways. Potential targets for CRS control by XBJ were predicted using network pharmacology, and the inhibitory effect of XBJ on the expression of relevant genes was verified using a macrophage model. Conclusion: The results of this study indicate that XBJ can enhance the killing effect of CAR-T cells on tumor cells and that the mechanism is related to the regulation of T cell proliferation and activation. Moreover, XBJ inhibited excessive inflammation associated with CAR-T therapy. However, the current findings remain to be further validated through in vivo experiments.

Background and objective Small cell lung cancer (SCLC) is known as recalcitrant cancer with high malignancy and heterogeneity. Immunotherapy has changed the treatment pattern of extensive-disease SCLC (ED-SCLC), but the beneficiary population is limited. Therefore, exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC. SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase M1 (PKM1) is one of the isozymes of PK, an important rate-limiting enzyme in glycolysis pathway. Previous studies have shown that PKM1 is related to autophagy and drug sensitivity, however, how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear. The aim of this study was to investigate the biological functions of PKM1 in SCLC, including its effects on proliferation, migration, autophagy, drug sensitivity, and expression of neuroendocrine (NE)-related markers in SCLC. Methods Western blot was used to detect the expression level of PKM1 in SCLC cells. PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection. Proliferation of cells and drug sensitivity were detected by MTT, and migration ability of cells was determined by Transwell. The level of autophagy was detected by flow cytometry. Western blot was used to determine the expression levels of NE-related proteins. Results PKM1 was differentially expressed among various SCLC cell lines, and was lower in H1092 cells (P

Abstract Background Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer’s, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. Methods Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1−/−) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. Results In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1−/− mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. Conclusions Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Abstract Background The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF. Methods Summary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study’s focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods. Results There was no significant effect of blood lipid traits on IPF risk (all P＞0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05–7.12, P = 0.039), 1.36 (1.02–1.82, P = 0.037), 1.66 (1.12–2.45, P = 0.011), 1.68 (1.14–2.48, P = 0.009), and 1.42 (1.20–1.67, P = 3.17×10-5), respectively. The SMR method identified a significant association between PCSK9 gene expression in whole blood and reduced IPF risk (OR = 0.71, 95% CI: 0.50–0.99, P = 0.043). Sensitivity analyses showed no evidence of bias. Conclusions Serum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation.

Binge-eating disorder (BED) is a type of eating disorder characterized by recurrent episodes of binge eating. Patients with BED have recurrent impulsive and out-of-controlled binge eating behavior, which can lead to gastrointestinal disorders, obesity, and the resulting metabolic and functional disorders of various systems and other physical problems; and it is also often co-morbid with affective disorder, anxiety disorders, substance use disorders, and other mental disorders, which need to be taken seriously. However, the recognition of BED in China was late, and it is difficult to achieve early identification and diagnosis, resulting in a prolonged course of disease. Therefore, under the organization of the Eating Disorders Coordination Group of the Psychosomatic Medicine Society of the Chinese Medical Association, together with the Eating Disorders Research Collaboration Group of the Psychiatric Medicine Society of the Chinese Medical Association, an expert group composed of 15 psychiatrists and evidence-based medicine experts, and 2 internal medicine experts, formulated this expert consensus based on evidence-based medical evidence, domestic and foreign guidelines and expert consensus, and expert experiences. The aim of this study is to improve the recognition, diagnosis and treatment of BED by psychiatrists, internists and general practitioners in China.

Abstract The characteristics and heterogeneity of coal pores are crucial for understanding the production mechanism of coalbed methane (CBM). In this study, coal samples with varying degrees of metamorphism (0.58% ≤ R O, max ≤ 3.44%) were collected. The characteristics of pore development and the heterogeneous properties of pores were revealed through low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR) experiments. The results indicate that pores with varying diameters exhibit favorable development in low-rank coals, along with favorable pores connectivity. The micropores composition of middle-rank coals was found to be 73.56%, however, the connectivity among transitional, meso, and macropores was observed to be poor. In high-rank coals, the proportion of micropores was 92.74%, with numerous micropores being closed or semi-closed. This resulted in inferior connectivity between micropores and transitional pores. As coal metamorphism progressed, the D L1 (characterizing the roughness of adsorption pores (AP) surface, ranging from 2.13 to 2.45) and D L2 (characterizing the complexity of AP structure, ranging from 2.56 to 2.77) initially decreased and then increased, whereas the D N (characterizing the heterogeneity of seepage pores (SP), ranging from 2.92 to 2.95) consistently improved. Furthermore, the roughness of pore surface and the complexity of pore structure in AP increased as the specific surface area and volume of pores increased. On the contrary, as the SP content increased, the uniformity of the pore structure improved. When the volume of SP remained constant, the complexity of the pore structure decreased due to increased pore connectivity.

Background: There is a strong causal relationship between intimate partner violence and major depressive disorder, which partly endangers women's safety across the life course and potentially affects the development of future generations. The international community has placed a high priority on addressing the intimate partner violence and the resulting burden of mental illness. Data collection needs to be captured across the temporal trend and spatial distribution for major depressive disorder attributed to intimate partner violence, to reflect the priorities and expectations of survivors.Method: This research obtained raw disability-adjusted life years (DALYs) information for major depressive disorder attributed to intimate partner violence from the Global Burden of Disease 2019. Using estimated annual percentage change and two-way fixed effects models, a secondary spatio-temporal analysis of the age-standardized DALYs rate from 1990 to 2019 was performed.Results: In 2019, DALYs lost among women experiencing major depressive disorder (3.16 million) accounted for 37.18% of the DALYs lost worldwide due to intimate partner violence. The age-standardized DALYs rate of major depressive disorder attributed to intimate partner violence was 108.57 per 100,000. The highest was concentrated in the menopausal transition (45-55), with 133.61 per 100,000, and particularly distributed in Uganda (429.31 per 100,000). The early reproductive period (15–19) showed the increasing age-standardized DALYs rate from 1990 to 2019, which was mainly driven by Malaysia (3.73% per year). Furthermore, countries with higher initial levels of the age-standardized DALYs rate were growing faster than those with lower levels.Conclusions: The burden of major depressive disorder attributed to intimate partner violence showed biological and spatial inequality, prioritized intervention should be targeted at vulnerable stage women in their early reproductive period and menopausal transition. Combined political, socio-cultural as well as medical measures to prevent violence and treat major depressive disorder should be implemented and developed.

Advances in foodomics have demonstrated the feasibility of detecting specific molecules, known as ‘foodomes’, that can serve as biomarkers in fresh meat and dairy products to identify the origin of feeding foods. Identifying these biomarkers is crucial to establish traceability, as consumers demand products of guaranteed quality. In this work, after conducting an exhaustive review of the most relevant scientific documents from the last twenty years, we present a collection of as many as 76 and 66 lipidomes, 42 and 14 metabolomes, 53 and 61 volatile compounds and 8 and 4 isotope ratios (from fresh meat and dairy products, respectively) as potential biomarkers to determine feeding regime in farm ruminants (e.g. fresh herbage, conserved forage or concentrate). CLA9cis-11trans, stearoyl-CoA desaturase, toluene, skatole, and δ13C and δ15N have been widely cited in scientific research to determine the feeding system in ruminants. A combination of these biomarkers with mathematical techniques (discriminant analysis and machine learning) could be used to determine origin and quality in meat and dairy products from ruminants.

Background The necessity of platinum-doublet chemotherapy in first-line immunotherapy for non-squamous non-small cell lung cancer (nsqNSCLC) with programmed death-ligand 1 (PD-L1) expression on less than 50% of tumor cells remains poorly investigated. Biomarkers predicting this necessity can guide chemotherapy-free treatment to minimize unnecessary toxicity.Methods Treated with immune checkpoint inhibitor monotherapy (ICI-mono), chemotherapy, or combination (ICI-chemo), 790 low PD-L1-expressing nsqNSCLCs (in-house: n=83; public: n=707) were analyzed for development and validation of the interaction score for additional chemotherapy (ISAC). Transcriptomic (public, n=11) and multiplex immunofluorescence data (in-house, n=100) were analyzed to evaluate the immune microenvironment.Results ICI-chemo, compared with ICI-mono, tended to prolong progression-free survival (PFS; HR=0.72, p=0.004) and overall survival (OS; HR=0.77, p=0.071) as first-line therapy in low PD-L1-expressing nsqNSCLCs. The added value of chemotherapy was observed in the ISAC-low subgroup (PFS: HR=0.48, p

IntroductionAkabane virus (AKAV) is a worldwide epidemic arbovirus belonging to the Bunyavirales order that predominantly infects livestock and causes severe congenital malformations. Reporter-expressing recombinant virus represents a powerful tool to characterize the viral biology in vitro and in vivo.MethodsIn this study, we have successfully established a reverse genetics system for AKAV. The recued virus possessed similar growth characteristics to the parental virus in vitro. Moreover, the recombinant AKAV reporter viruses expressing nanoluciferase (Nluc) or mWasabi were constructed by inserting into S segment, named rAKAV-Nluc and rAKAV-mWasabi, respectively.ResultsWe investigated the virological characteristics of rAKAV-Nluc and rAKAV-mWasabi and found that rAKAV-Nluc displayed similar growth kinetics as the parental virus and could stably produce the nano-luciferase even after 10 rounds of serial passages. rAKAV-mWasabi also exhibited comparable growth kinetics and genetic stability as the parental virus. We further used the two reporter viruses to test the susceptibility of different cell lines to AKAV and found that cell lines derived from various host species, including human, swine, cattle, and monkey enables AKAV replication efficiently, accelerating our understanding of the AKAV cell tropism range.DiscussionTaken together, our established reverse genetics system for AKAV provides more convenient screening tools and can be used to study AKAV virulence and tropism, and to elucidate the molecular biology of AKAV.

IntroductionThe occurrence of pachyonychia congenita (PC) and acne inversa (AI) may be related to gene mutations. The aim of this study is to identify the genetic cause in a patient with PC and AI, and to explore the possible molecular mechanism of their co-occurrence.MethodsThe clinical data of the proband were collected, and the genomic DNA of the proband and unaffected parents were extracted. The variant sites of the proband were identified by whole-exome sequencing, and then the variant sites of the proband and his parents were verified by Sanger sequencing.ResultsA heterozygous variant in KRT17 gene was found in the patient, resulting in a missense amino acid variant (p.N92D). The variant was not found in his parents or 100 unrelated healthy controls. In addition, this variant was not found in the gnomad v4 database. The three-dimensional structure analysis of the protein suggested that the polarity of amino acids changed after the variant. After lentiviral plasmid transfection into HaCaT cells, the expression level of NOTCH signaling decreased in the constructed c.274A>G (p.Asn92Asp) of KRT-17 mutant cells compared to that in the wild-type. Subsequent verification confirmed that differences in the expression levels of p-PI3K, AKT and p-AKT between the groups were not statistically significant.DiscussionAlthough this variant has been reported previously, our findings could expand the spectrum of co-occurrence of PC and AI with KRT17 gene variants, and elucidated the possible pathogenesis at the protein level, thereby laying a foundation for the genetic diagnosis and genetic counseling provided to individuals with PC.

To investigate the functioning mechanism of cruise altitude on transportation and discharging dynamics of onboard fire-extinguishants, a numerical model coupling the vaporization and flowing process is established for the Halon 1301-N2 multi-component two-phase flow inside the onboard fire-extinguishing system based on computational fluid dynamics. Flowing and transportation parameters are simulated and compared for Halon 1301 at 0 m, 3000 m, 6000 m and 12000 m. Moreover, the peak discharging fluid pressure, velocity and density are also analyzed to evaluate the impact of altitude on discharging dynamics of Halon 1301. Notably, the maximum discharging velocity at 3000 m, 6000 m and 12000 m are reduced by 4 %, 9 % and 15 % relative to that at 0 m; the maximum discharging fluid pressure and density at 12000 m are respectively reduced by 32 % and 12 % relative to those at 0 m. High altitude is unraveled to inhibit the vaporization of Halon 1301 and lower the discharging efficiency at the pipeline outlet, consequently lowering the diffusion efficiency and effective concentration of Halon 1301 in the protected area and further weakening the fire-suppression effectiveness. The unveiled insights afford guidance for the optimization of fire-extinguishing systems to improve the fire-fighting capability of airplanes at high altitudes.

Renal calculi weighing over 200 g are relative rare in modern urological practice since most stones might cause renal dysfunction before reaching such size. We here reported an extremely rare case of giant stones in single kidney of a 72-year-old Chinese male patient who had 30 years long-term history of lithiasis in the right kidney. These huge kidney stones, total weight 832.6 g were successfully removed with multiple sessions of surgery. Kidney function was relatively stable after long-term medical care in primary care centers. Timely treatment of kidney stones early should arouse more attention worldwide.

A model kit consisting of magnetic rods and steel balls, which is generally sold as a desktop toy, has been utilized to construct physical models for teaching packing arrangements of metallic crystal. All four basic metallic crystal structure models are easily constructed layer by layer, and corresponding unit cells can be naturally derived from the packing structures. The low-cost models based on magnetic rods and steel balls are portable and easy-to-construct, and teaching practice shows that they can guide students to gain a deeper understanding of packing arrangements of metallic crystal. Positive feedback from students indicates that they are interested in constructing models with the rods and balls by themselves. Overall, compared with the existing crystal structure models, these models combine the characteristics of portability, low cost, and ease of construction; therefore, they have great potential to enhance students' learning of metallic crystal structures through hands-on activities or classroom demonstrations.

Abstract Background Acinetobacter lwoffii (A.lwoffii) is a serious zoonotic pathogen that has been identified as a cause of infections such as meningitis, bacteremia and pneumonia. In recent years, the infection rate and detection rate of A.lwoffii is increasing, especially in the breeding industry. Due to the presence of biofilms, it is difficult to eradicate and has become a potential super drug-resistant bacteria. Therefore, eradication of preformed biofilm is an alternative therapeutic action to control A.lwoffii infection. The present study aimed to clarify that baicalin could eradicate A.lwoffii biofilm in dairy cows, and to explore the mechanism of baicalin eradicating A.lwoffii. Results The results showed that compared to the control group, the 4 MIC of baicalin significantly eradicated the preformed biofilm, and the effect was stable at this concentration, the number of viable bacteria in the biofilm was decreased by 0.67 Log10CFU/mL. The total fluorescence intensity of biofilm bacteria decreased significantly, with a reduction rate of 67.0%. There were 833 differentially expressed genes (367 up-regulated and 466 down-regulated), whose functions mainly focused on oxidative phosphorylation, biofilm regulation system and trehalose synthesis. Molecular docking analysis predicted 11 groups of target proteins that were well combined with baicalin, and the content of trehalose decreased significantly after the biofilm of A.lwoffii was treated with baicalin. Conclusions The present study evaluated the antibiofilm potential of baicalin against A.lwoffii. Baicalin revealed strong antibiofilm potential against A.lwoffii. Baicalin induced biofilm eradication may be related to oxidative phosphorylation and TCSs. Moreover, the decrease of trehalose content may be related to biofilm eradication.

Highlights Evaporation and solution two-step hybrid process are used to fabricate conformal growth of perovskite film on textured silicon substrates. F-PMAI additive enlarged the perovskite grains, induced the (111) preferred orientation and passivated interface defects. We obtained a champion efficiency of 30.05% for a monolithic perovskite/silicon tandem solar cell based on a silicon thin film tunneling junction.

ObjectiveTo analyze the family food environment of students in key monitoring counties of the Nutrition Improvement Program for Rural Compulsory Education Students in Henan province in 2021, to provide data support for further strengthening nutrition education. MethodsThe study participants were 5 682 students from 20 primary schools and 20 secondary schools selected by stratified random cluster sampling in five key monitoring counties of the Nutrition Improvement Program for Rural Compulsory Education Students in Henan province. Students were measured for height and weight in 2021, and their parents were anonymously surveyed on-site using a questionnaire developed by researchers at the Chinese Center for Disease Control and Prevention on knowledge and behaviors related to child nutrition and health. ResultsAmong the parents of 5 673 students with valid data, the awareness rate of child nutrition and health knowledge was 68.94% and the prevalence rate of behaviors related to child nutrition and health was 26.65%. The detection rate of overweight and obesity among students was 27.38%. There were 55.37% of parents who reported accurate perception on their children's body size, but 41.62% of parents underestimated their children's body size, and parents' biased perception on children's body size was not related to their knowledge and practices related to child nutrition and health. The agreement between parents' perception of children's body type and the measurement based body size assessment was poor (Kappa = 0.203, P < 0.001). Conclusion In the key monitoring counties of the Nutrition Improvement Program for Rural Compulsory Education Students in Henan province, the awareness rate of child nutrition and health knowledge among parents of primary and secondary school students is relatively high, but the prevalence of child nutrition and health behaviors and accurate perception of their children's body size are low, indicating a gap between knowledge and practice. Parents of students generally underestimate their children's body size, which is not conducive to controlling overweight and obesity among students.

Constructing the magnesium alloy with fine grains, low density of dislocations, and weak crystal orientation is of crucial importance to enhance its comprehensive performance as the anode for Mg-air battery. However, this unique microstructure can hardly be achieved with conventional plastic deformation such as rolling or extrusion. Herein, we tailor the microstructure of Mg-Al-Sn-RE alloy by using the friction stir processing, which obviously refines the grains without increasing dislocation density or strengthening crystal orientation. The Mg-air battery with the processed Mg-Al-Sn-RE alloy as the anode exhibits higher discharge voltages and capacities than that employing the untreated anode. Furthermore, the impact of friction stir processing on the electrochemical discharge behaviour of Mg-Al-Sn-RE anode and the corresponding mechanism are also analysed according to microstructure characterization and electrochemical response.

Metal halide perovskite has generated significant attention due to its high optical absorption coefficient, the tunability of bandgap, and its solution processing properties, all of which have led to a range of applications including solar cells, photodetectors, light-emitting diodes and lasers. However, the material's application as an optical modulator for high-energy ultrafast lasers is still limited by its slow nonlinear optical response, low damage threshold and the inferior stability. Herein, we developed a saturable absorber (SA) with the thermally stable Cs0.15FA0.85PbI2.85Br0.15 perovskite thin films as an optical modulator towards the near-infrared nanosecond passively Q-switched Nd:YAG laser generation for the first time. The Cs0.15FA0.85PbI2.85Br0.15 perovskite SA optical modulator produced an exceptional nonlinear optical response with a notable modulation depth of 15.1%, an ultrashort recovery time of 52.46 ps, and a high optical damage threshold exceeding 275.9 mJ/cm2. Of further significance, it displayed an excellent operational stability, and when incorporated into the oscillator of the Nd:YAG laser, allowed for a stable operation of 166 ns pulse laser with a center wavelength of 1.06 μm. The findings provide a pathway for the employment of the Cs0.15FA0.85PbI2.85Br0.15 perovskite SA optical modulator in near-infrared ultrafast laser applications.

High levels of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) have been associated with tumor aggressiveness and drug resistance in several cancer types. Nevertheless, the mechanistic role of BCAT1 in T-cell acute lymphoblastic leukemia (T-ALL) remains uncertain. We provide evidence that Bcat1 was over-expressed following NOTCH1-induced transformation of leukemic progenitors and that NOTCH1 directly controlled BCAT1 expression by binding to a BCAT1 promoter. Further, using a NOTCH1 gain-of-function retroviral model of T-ALL, mouse cells genetically deficient for Bcat1 showed defects in developing leukemia. In murine T-ALL cells, Bcat1 depletion or inhibition redirected leucine metabolism towards production of 3-hydroxy butyrate (3-HB), an endogenous histone deacetylase inhibitor. Consistently, BCAT1 depleted cells showed altered protein acetylation levels which correlated with a pronounced sensitivity to DNA damaging agents. In human NOTCH1-dependent leukemias, high expression levels of BCAT1 may predispose to worse prognosis. Therapeutically, BCAT1 inhibition specifically synergized with etoposide to eliminate tumors in patient-derived xenograft models suggesting that BCAT1 inhibitors may have a part to play in salvage protocols for refractory T-ALL.

ObjectiveFibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density.MethodsWe conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results.ResultsMR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively.ConclusionsOur study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Chloroprocaine and lidocaine bicarbonate are commonly used for epidural anesthesia because of their rapid onset, particularly in the case of conversion from epidural labor analgesia to emergency cesarean section. However, it is unclear whether lidocaine bicarbonate combined with fentanyl has an advantage over chloroprocaine alone in emergency cesarean section. In this study, 102 women who underwent elective cesarean section received 15 mL 3% chloroprocaine and 1 mL saline (CP group) or 15 mL 1.73% lidocaine bicarbonate and 1 mL fentanyl 50 μg (LF group) for epidural anesthesia. Nociceptive block level was assessed by pinprick and recorded every minute. The primary outcome was the onset time to T6 block. The median onset time to T6 analgesia was 10 [10, 10] min in the CP group and 10 [7, 10] min in the LF group (COX model for CP versus LF, HR 0.47, 95% CI 0.23–0.95, p = 0.035). The median onset time to T8 analgesia was 7 [5, 9] min in CP group and 5 [4, 7] min in LF group (COX model for CP versus LF, HR 0.61, 95% CI 0.39–0.95, p = 0.027). The proportion of hypotension episodes occurring before delivery in LF group was lower than that in CP group (p = 0.011). The incidence of block level ≥ T4 after supplemental dosing in the LF group was lower than that in the CP group (p = 0.031). Compared with 3% chloroprocaine, 1.73% lidocaine bicarbonate combined with fentanyl 50 μg has a slightly faster onset time and less hypotension in epidural anesthesia for cesarean section.Clinical Trial Registration:http://www.chictr.org.cn/index.html, identifier ChiCTR2200056180.

Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development.

Axon projection is a spatial- and temporal-specific process in which the growth cone receives environmental signals guiding axons to their final destination. However, the mechanisms underlying changes in axonal projection direction without well-defined landmarks remain elusive. Here, we present evidence showcasing the dynamic nature of axonal projections in Drosophila’s small ventral lateral clock neurons (s-LNvs). Our findings reveal that these axons undergo an initial vertical projection in the early larval stage, followed by a subsequent transition to a horizontal projection in the early-to-mid third instar larvae. The vertical projection of s-LNv axons correlates with mushroom body calyx expansion, while the s-LNv-expressed Down syndrome cell adhesion molecule (Dscam1) interacts with Netrins to regulate the horizontal projection. During a specific temporal window, locally newborn dorsal clock neurons secrete Netrins, facilitating the transition of axonal projection direction in s-LNvs. Our study establishes a compelling in vivo model to probe the mechanisms of axonal projection direction switching in the absence of clear landmarks. These findings underscore the significance of dynamic local microenvironments in the complementary regulation of axonal projection direction transitions.