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Abstract Effective detection is critical for terahertz applications, yet it remains hindered by the unclear mechanisms that necessitate a deeper understanding of photosensitive materials with exotic physical phenomena. Here, we investigate the terahertz detection capabilities of the two-dimensional antiferromagnetic semimetal NbFeTe2. Our study reveals that the interaction between antiferromagnetic magnetic moments and electron spin induces disordered carriers to hop between localized states, resulting in a nonlinear increase in responsivity as temperature decreases. We integrate asymmetric electrodes to generate a sufficient Seebeck potential, enabling carriers to overcome the barrier of localized states and achieve reordering at room temperature. Additionally, the self-powered performance of the NbFeTe₂/graphene heterojunction is optimized by the built-in electric field, achieving peak responsivity of 220 V W-1 and noise equivalent power of

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

Abstract Elaborating and understanding disparities in the burden of cardiovascular disease attributable to high fasting plasma glucose is important to improve diabetes prevention and promote cardiovascular health. In this study, we pool data on 791,373 people aged 25 years and older from three population-based surveys, and estimate the burden of cardiovascular disease attributable to high fasting plasma glucose between 2010 and 2018 in China by age, sex, region and socio-demographic index. In 2018, an estimated total of 498.61 thousand (95% uncertainty interval 463.93 to 534.12) cardiovascular disease-related deaths are attributable to high fasting plasma glucose in China. High fasting plasma glucose accounts for 1076.09 years of life lost per 100,000 people (95% uncertainty interval 1026.88–1129.04) due to cardiovascular disease in 2018, with substantial variation across provinces. In 2018, the higher age-standardised cardiovascular disease mortality rate attributable to high fasting plasma glucose is observed in the high-middle socio-demographic index region and the middle socio-demographic index region. Nationally, compared to 2010, exposure to high fasting plasma glucose and population aging in 2018 are the primary drivers of increased fasting plasma glucose-related deaths due to cardiovascular disease. Findings of this study emphasize the importance of developing population-specific tailored measures in China and other regions with similar condition.

Halomonas bluephagenesis TD serves as an exceptional chassis for next generation industrial biotechnology to produce various products. However, the simultaneous editing of multiple loci in H. bluephagenesis TD remains a significant challenge. Herein, we report the development of a multiple loci genome editing system, named CRISPR-deaminase-assisted base editor (CRISPR-BE) in H. bluephagenesis TD. This system comprises two components: a cytidine (CRISPR-cBE) and an adenosine (CRISPR-aBE) deaminase-based base editor. CRISPR-cBE can introduce a cytidine to thymidine mutation with an efficiency of up to 100 % within a 7-nt editing window in H. bluephagenesis TD. Similarly, CRISPR-aBE demonstrates an efficiency of up to 100 % in converting adenosine to guanosine mutation within a 7-nt editing window. CRISPR-cBE has been further validated and successfully employed for simultaneous multiplexed editing in H. bluephagenesis TD. Our findings reveal that CRISPR-cBE efficiently inactivated all six copies of the IS1086 gene simultaneously by introducing stop codon. This system achieved an editing efficiency of 100 % and 41.67 % in inactivating two genes and three genes, respectively. By substituting the Pcas promoter with the inducible promoter PMmp1, we optimized CRISPR-cBE system and ultimately achieved 100 % editing efficiency in inactivating three genes. In conclusion, our research offers a robust and efficient method for concurrently modifying multiple loci in H. bluephagenesis TD, opening up vast possibilities for industrial applications in the future.

Herein, the effect of fluoropolymer binders on the properties of polymer-bonded explosives (PBXs) was comprehensively investigated. To this end, fluorinated semi-interpenetrating polymer networks (semi-IPNs) were prepared using different catalyst amounts (denoted as F23-CLF-30-D). The involved curing and phase separation processes were monitored using Fourier-transform infrared spectroscopy, differential scanning calorimetry, a haze meter and a rheometer. Curing rate constant and activation energy were calculated using a theoretical model and numerical method, respectively. Results revealed that owing to its co-continuous micro-phase separation structure, the F23-CLF-30-D3 semi-IPN exhibited considerably higher tensile strength and elongation at break than pure fluororubber F2314 and the F23-CLF-30-D0 semi-IPN because the phase separation and curing rates matched in the initial stage of curing. An arc Brazilian test revealed that F23-CLF-30-D-based composites used as mock materials for PBXs exhibited excellent mechanical performance and storage stability. Thus, the matched curing and phase separation rates play a crucial role during the fabrication of high-performance semi-IPNs; these factors can be feasibly controlled using an appropriate catalyst amount.

Given that input-based language and literacy environments provide socioculturally-enriched contexts for bilingual and biliteracy acquisition, the current study aims to explore the contribution of early input in various sociocultural contexts to later biliteracy development among ­college-level Chinese heritage language (CHL) students. A group of CHL students (N = 195) participated in this study and completed a background survey about their early oral and print experiences in different sociocultural contexts. Biliteracy measurements including Chinese-English bilingual morphological awareness and reading ability were administered to the participants. Drawing on multivariate analyses, the study verified both intralingual and interlingual contributions of input-based experiences to biliteracy development. The study suggests that (1) community and after-school language and literacy support can have a long-term impact on the maintenance of heritage language literacy skills. (2) heritage language input experiences do not create obstacles for dominant language literacy development. (3) heritage language literacy input provides facilitations for the abstraction of bilingual structures and units.

Introduction Despite its therapeutic advantages, postmastectomy radiotherapy (PMRT) increases the risk of complications and often leads to poor cosmesis in women undergoing breast reconstruction. Preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction is technically feasible, with low rates of surgical complications and good short-term oncological outcomes. Further evaluation in a randomised trial comparing preoperative radiotherapy versus conventional PMRT in breast reconstruction is required to assess both oncological and patient-reported outcomes (PROs).Methods and analysis The CAPPELLA trial is a prospective, multicentre, open-label, randomised controlled trial across nine centres comparing PROs and safety outcomes between preoperative and postoperative radiotherapy in patients with locally advanced breast cancer requiring immediate DIEP flap reconstruction. Female patients aged >18 years with breast cancer who are treated with neoadjuvant systemic treatment, require both mastectomy and radiotherapy and are suitable for DIEP flap reconstruction will be included. Patients will be randomly assigned (1:1) to a preoperative radiotherapy group or a postoperative radiotherapy group. Stratification will be performed by cancer centre at initial diagnosis. The radiation volumes will include the ipsilateral breast/chest wall, supraclavicular lymph nodes, undissected axilla and internal mammary nodes. The dose regimen will be 42.56 Gy in 16 fractions. The primary endpoint will be satisfaction with the breast domain of the BREAST-Q at 2 years postoperatively. The secondary endpoints will include PROs at 3, 12 and 24 months postoperatively in both groups, aesthetic assessment, complication rates, rates of total pathological complete response (tpCR) and tumour safety. All patients will be followed up for 36 months postoperatively. The app software will be used to collect all data prospectively. Data will be analysed using SPSS and Stata software. The target sample size will be 80 participants.Ethics and dissemination This study will be performed according to the Helsinki Declaration. All patients will be asked to provide informed consent before enrolment. Approval for this study was provided by the independent ethics committee and institutional review board of Fudan University Shanghai Cancer Centre. We will present the study results at national and international meetings and publish them in a scientific peer-reviewed journal.Trial registration number NCT05512286.

Constructed wetland (CW) technology has attracted much attention due to its economical and environmentally friendly features. The low dissolved oxygen (DO) and low carbon/nitrogen (C/N) ratio in the wetland influent water affect the treatment performance of CW, resulting in a decrease in the removal efficiency of ammonia nitrogen (NH4+-N) and nitrate nitrogen (NO3−-N). In order to address this problem, this study optimized the pollutants removal performance of unsaturated vertical flow constructed wetland (UVFCW) by adding sustained-release carbon sources (corn cobs + polybutylene adipate terephthalate (PBAT)). The results showed that the sustained-release of carbon source increased the carbon source in UVFCW, thus increasing the abundance and activity of denitrifying microorganisms and enhancing the denitrification reaction, ultimately improving the removal of NO3−-N, with its removal efficiency reaching up to 95.50%. The placement method of sustained-release carbon source mainly affected the distribution of carbon source and DO in water body, thus influencing the relative abundance of microorganisms, finally affecting the removal of pollutants. Among them, the removal efficiency of total nitrogen (TN), NO3−-N, and total phosphorus (TP), and the relative abundance of denitrifying microorganisms in the CWR-Cu (uniform placement of sustained-release carbon source) were significantly higher than those in the CWR-Ca (centralized placement above) and CWR-Cb (centralized placement below) (p < 0.05). The surface C:O (carbon:oxygen) ratio of sustained-release carbon source after water treatment showed a decreasing trend, and CWR-Cu exhibited the greatest decrease in C:O ratio. In summary, CWR-Cu achieved the highest utilization of the carbon source and produced the largest number of heterotrophic microorganisms. This study reveals that CWR-Cu is a structural process for the efficient removal of nitrogen and phosphorus pollutants, and our findings provide theoretical basis and technical support for actual projects.

Abstract Vancomycin (VAN)‐intermediate Staphylococcus aureus (VISA) is a critical cause of VAN treatment failure worldwide. Multiple genetic changes are reportedly associated with VISA formation, whereas VISA strains often present common phenotypes, such as reduced autolysis and thickened cell wall. However, how mutated genes lead to VISA common phenotypes remains unclear. Here, we show a metabolism regulatory cascade (CcpA‐GlmS), whereby mutated two‐component systems (TCSs) link to the common phenotypes of VISA. We found that ccpA deletion decreased VAN resistance in VISA strains with diverse genetic backgrounds. Metabolic alteration in VISA was associated with ccpA upregulation, which was directly controlled by TCSs WalKR and GraSR. RNA‐sequencing revealed the crucial roles of CcpA in changing the carbon flow and nitrogen flux of VISA to promote VAN resistance. A gate enzyme (GlmS) that drives carbon flow to the cell wall precursor biosynthesis was upregulated in VISA. CcpA directly controlled glmS expression. Blocking CcpA sensitized VISA strains to VAN treatment in vitro and in vivo. Overall, this work uncovers a link between the formation of VISA phenotypes and commonly mutated genes. Inhibition of CcpA‐GlmS cascade is a promising strategy to restore the therapeutic efficiency of VAN against VISA infections.

ABSTRACTIn contrast to traditional intermetallics that are difficult to process and prone to cracking during additive manufacturing, our work demonstrates the successful fabrication of crack-free, high-performance CCIMAs via electron beam powder bed fusion (EBPBF). The microstructures of CCIMAs (NiCoFeAlTiB) fabricated by EBPBF are remarkably complex, exhibiting a multiphase composition where the disordered FCC phase forms the matrix interleaved with L12-ordered intermetallic phase. The unique combination of ordered lattices and high-entropy disordered phases, tuned by optimised EBPBF processing, imparts exceptional mechanical properties with a high tensile strength (∼1 GPa) and a sufficient ductility (∼11%). It is found that additional minor HCP and L21 precipitates can also effectively slow down and block the crack extension. This work demonstrates a pathway for crack-free fabrication of CCIMAs with tailored microstructures using EBPBF which may provide new insights and manufacturing strategies to unlock the potential of these advanced intermetallic alloys.

Abstract Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

Abstract Background Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades. Aims To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats. Methods Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined. Results The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application. Conclusions ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.

Abstract Introduction The health impact of retirement is controversial. Most previous studies have been based on self-reported health indicators or the endpoints of some chronic diseases (e.g., morbidity or mortality), but objective physiological indicators (e.g., blood pressure) have rarely been used. The objective of this study is to elucidate the health effects of retirement on blood pressure, thereby offering empirical evidence to facilitate the health of retirees and to optimize retirement policies. Methods From 2012 to 2015, 84,696 participants of the Chinese Hypertension Survey (CHS) were included in this study. We applied the fuzzy regression discontinuity design (FRDD) to identify retirement’s causal effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure. We also explored the heterogeneity in the effects of retirement across different sex and education level groups. Results Based on the fully adjusted model, we estimated that retirement increased SBP by 5.047 mm Hg (95% CI: -2.628-12.723, P value: 0.197), DBP by 0.614 mm Hg (95% CI: -3.879-5.108, P value: 0.789) and pulse pressure by 4.433 mm Hg (95% CI: -0.985-9.851, P value: 0.109). We found that retirement led to a significant increase in male participants’ SBP and pulse pressure as well as a possible decrease in female participants’ blood pressure. Additionally, the blood pressure levels of low-educated participants were more vulnerable to the shock of retirement. Conclusion Retirement is associated with an increase in blood pressure level. There is a causal relationship between the increase in blood pressure levels of men and retirement. Policy-makers should pay extra attention to the health status of men and less educated people when adjusting retirement policies in the future.

Coastal wetlands are the main distribution of blue carbon in coastal zones and well known for their high carbon sequestration capacity. Investigating the variation of carbon budget is crucial for understanding the functionality of coastal wetlands and effectively addressing climate change. In this study, a bibliometric analysis of 4,509 articles was conducted to reveal research progress, hot issues, and emerging trends in the coastal wetland carbon budget field. The number of publications and citations in this field increased exponentially from 1991 to 2022. The leading subject category was Environmental Sciences with 1,844 articles (40.9%). At present, studies have been focused on blue carbon, the effects of climate change and man-made disturbances on carbon cycle, and the restoration of coastal wetlands. Based on the hotspots and trends in this field, the future researches should include (1) exploring the functional mechanisms of various factors affecting carbon cycle and establishing a methodological system for the estimation of blue carbon in coastal wetlands; (2) researching restoration techniques of coastal wetland and constructing wetland restoration evaluation index system; and (3) formulating enforceable carbon trading policy and strengthening international cooperation. HIGHLIGHTS Bibliometric analysis of the carbon budget of coastal wetlands was conducted.; The number of publications and citations increased exponentially from 1991 to 2022.; Research hotspots of coastal wetlands shifted from greenhouse gases to blue carbon.; More attention should be paid to restoration techniques of coastal wetlands.;

Abstract The study of the outcomes of critically ill patients has been a hard stuff in the field of intensive care. To explore the relationship between changes of severity scores, bioelectrical impedance analysis (BIA) and outcomes of critically ill patients, we enrolled patients (n = 206) admitted to intensive care unit (ICU) in Jinling Hospital from 2018 to 2021 with records of BIA on the days 1- and 3- ICU. Collected BIA and clinical data including simplified acute physiology score II (SAPS II) and sequential organ failure assessment. According to the baseline and change of severity scores or phase angle (PA) values, the patients were divided into: G–G, baseline good status, 3rd day unchanged; G–B, baseline good status, 3rd day deteriorated; B–G, baseline bad status, 3rd day improved; and B–B, baseline bad status, 3rd day unchanged. According to PA, the mortality of group G–G was 8.6%, and it was greater than 50% in group B–B for severity scores. The new score combining PA and severity scores established. Multivariate logistic regression analysis revealed that PA–SAPS II score was the only independent factor for 90-day mortality (P

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

Bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) are used in consumer products; however, their toxic effects on intestinal epithelium remain largely unknown. In this study, we combined intestinal organoids and single-cell RNA sequencing to investigate the impact of BPA and BHPF exposure on intestinal cell composition, differentiation, and function. Both compounds inhibited the growth of small intestinal organoids, with BHPF exhibiting a more potent inhibitory effect. BPA and BHPF did not significantly alter the overall cell type composition; however, they led to different alterations in cell–cell communications. Gene Ontology enrichment analysis showed that BPA and BHPF exposures affected various biological processes, such as glutathione transferase activity, antioxidant activity, and lipid metabolism, in cell type-specific and compound-dependent manners. Trajectory analysis demonstrated that BPA and BHPF altered the differentiation trajectory of the intestinal cells. To further connect the cellular mechanism to the phenotypic impact in vivo, we constructed a mouse model exposed to BPA or BHPF and observed significant alterations in intestinal morphology, including reduced crypt depth and villus length and impaired stem cell proliferation and self-renewal. These results provide novel insights into the cell type-specific effects of BPA and BHPF on the intestinal epithelium and highlight the potential risks of exposure to these compounds. Our findings underscore the importance of evaluating the safety of BPA substitutes and contribute to a better understanding of the effects of environmental chemicals on gut health.

ABSTRACT Background Dexamethasone (Dex), a synthetic glucocorticoid that acts by binding to the glucocorticoid receptor (GR), has been widely applied to treat leukemia and lymphoma; however, the precise mechanism underlying Dex action is still not well elucidated. DOT1L, a histone H3‐lysine79 (H3K79) methyltransferase, has been linked to multiple cancer types, particularly mixed lineage leukemia (MLL) gene rearranged leukemia, but its contribution to lymphoma is yet to be delineated. Analysis from the TCGA database displayed that DOT1L was highly expressed in lymphoma and leukemia. Results We initially demonstrated that DOT1L served as a new target gene controlled by GR, and the downregulation of DOT1L was critical for the killing of B‐lymphoma cells by Dex. Further study revealed that Dex had no impact on the transcriptional activity of the DOT1L promoter, rather it reduced the mRNA level of DOT1L at the posttranscriptional level. In addition, knockdown of DOT1L remarkably inhibited the B‐lymphoma cell growth. Conclusions Overall, our findings indicated that DOT1L may serve as a potential drug target and a promising biomarker of Dex sensitivity when it comes to treating B lymphoma.

Thymosin beta 10 (TMSB10) overexpression is a general characteristic in human carcinogenesis. It is involved in the malignant process of generating multiple cancers. However, there are only a few reports about TMSB10 in colorectal cancer (CRC) and the mechanism of its carcinogenetic effect is still poorly understood. The present study intends to clarify the biological roles and carcinogenic mechanism of TMSB10 in CRC and to explore the possibility whether TMSB10 might be useful as a non-invasive serum tumor biomarker in detecting CRC. Immunohistochemical results showed that TMSB10 protein expression in CRC tissues was generally higher than that in adjacent tissues, and the TMSB10 contents in serum of CRC patients was significantly elevated compared to that of healthy controls. Knockdown-TMSB10 increased apoptosis and induced S-cell cycle arrest, and finally inhibited cell proliferation in vitro and in vivo. Transcriptome sequencing and western blotting analysis revealed that knockdown-TMSB10 increased phosphorylation of p38 and activated the p38 pathway that blocked cell cycle and promoted apoptosis. Taken together, our study indicated that TMSB10 could serve as a minimally invasive serum tumor marker in detecting CRC. At the same time it demonstrates an effective regulatory capacity of TMSB10 on cell proliferation of CRC, suggesting that TMSB10 and downstream effector molecules regulated by TMSB10 could further be applied as an appealing target in clinical post-surgery chemotherapy.

Abstract Background Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. Methods This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. Results No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483–3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987–1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999–1.011, P-value = 0.132). Conclusion This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Abstract Background Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. Results In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Conclusions Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

Abstract The Pacific Decadal Oscillation (PDO), renowned as the dominant sea surface temperature (SST) fluctuation in the North Pacific and extensively scrutinized for its extensive influence on global climate patterns, stands in stark contrast to the Victoria mode (VM). Traditionally, the VM, representing the second most prominent SST pattern in the North Pacific, has not garnered comparable attention. However, our investigation unveils a remarkable surge in the low-frequency VM variability, spanning periods greater than 8 years, over the course of a century. Astonishingly, this enhanced VM variability now surpasses the PDO’s variability in recent decades, signifying a notable shift. Consequently, the heightened VM variability assumes newfound significance in shaping climate systems across the entire North Pacific region and in distant locales. This intensified VM behavior could be attributed to amplified atmospheric variability in the Hawaiian region, primarily stemming from the reinforced variability in the tropical central Pacific (CP) SST in recent decades. As greenhouse warming escalates CP SST variability, the VM’s enhanced variability may further intensify, yielding broader and more profound repercussions in the future.

Abstract In 2023, the development of El Niño is poised to drive a global upsurge in surface air temperatures (SAT), potentially resulting in unprecedented warming worldwide. Nevertheless, the regional patterns of SAT anomalies remain diverse, obscuring where historical warming records may be surpassed in the forthcoming year. Our study underscores the significant influence of El Niño and the persistence of climate signals on the inter-annual variability of regional SAT, both in amplitude and spatial distribution. The likelihood of global mean SAT exceeding historical records, calculated from July 2023 to June 2024, is estimated at 90%, contingent upon annual-mean sea surface temperature anomalies in the eastern equatorial Pacific exceeding 0.6 °C. Regions particularly susceptible to recording record-high SAT include coastal and adjacent areas in Asia such as the Bay of Bengal and the South China Sea, as well as Alaska, the Caribbean Sea, and the Amazon. This impending warmth heightens the risk of year-round marine heatwaves and escalates the threat of wildfires and other negative consequences in Alaska and the Amazon basin, necessitating strategic mitigation measures to minimize potential worst-case impacts.

Abstract Structurally colored composite films, composed of orderly arranged colloids in polymeric matrix, are emerging flexible optical materials, but their production is bottlenecked by time-consuming procedures and limited material choices. Here, we present a mild approach to producing large-scale structurally colored composite films by shearing supramolecular composites composed of polymers and colloids with supramolecular interactions. Leveraging dynamic connection and dissociation of supramolecular interactions, shearing force stretches the polymer chains and drags colloids to migrate directionally within the polymeric matrix with reduced viscous resistance. We show that meter-scale structurally colored composite films with iridescence color can be produced within several minutes at room temperature. Significantly, the tunability and diversity of supramolecular interactions allow this shearing approach extendable to various commonly-used polymers. This study overcomes the traditional material limitations of manufacturing structurally colored composite films by shearing method and opens an avenue for mildly producing ordered composites with commonly-available materials via supramolecular strategies.

Physical symptoms plague construction workers and pose threats to safety performance and productivity. Following the resilience engineering (RE) principles, recent construction safety management practices enhance construction workers’ safety capability and safety management system resilience. This paper established an exploratory structural model explaining how construction workers’ safety capability alleviates their physical and psychological symptoms through safety management system resilience. To validate and estimate the structural model, 741 valid responses from construction workers based in Shanghai, China were obtained. Given no established scales for the constructs in the model, a cross-validation procedure, consisting of exploratory and confirmatory factor analysis and path analysis, was performed. The results showed that although neither safety capability nor safety management system resilience has direct negative impacts on physical symptoms, they can reduce physical symptoms via alleviating psychological symptoms. Furthermore, safety capability can reduce psychological and physical symptoms via safety management system resilience. This paper therefore suggests that cultivating construction workers’ safety capability would be the first step in implementing resilience engineering principles in construction. The continuous implementation of cost-effective and tailored resilience training programs are suggested to enhance construction workers’ safety capability. Safety management systems are suggested to improve with the fostering of a just culture and emerging technologies.

Abstract Coastal El Niño is an extreme situation of El Niño‐Southern Oscillation (ENSO) with sea surface temperature warming confined in the far‐eastern equatorial Pacific. Some coastal El Niños evolve into a basin scale El Niño, and some don't, implying a diversity in ENSO evolutions after a coastal El Niño event. In this study, the coastal El Niños in 2017 and 2023 are selected to examine their subsequent evolution. Both coastal El Niños developed after a La Niña, with the former followed by a La Niña and the latter by a basin‐scale El Niño. The cold (warm) subsurface temperatures in 2017 (2023) were key factors leading to the divergent ENSO evolution. Convection over the western tropical Pacific and the atmospheric circulation anomalies across the equatorial Pacific also contributed to the differences. Model predictions suggest that differences in ENSO evolution after a coastal El Niño are associated with differences in ENSO predictability.

Abstract Background Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. Methods BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. Results MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. Conclusions MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.

Aiming at the problems of low efficiency of minor repair and maintenance of military equipment in the synthetic force, strong randomness of maintenance human resource allocation, and unbalanced and unreasonable resource utilization, taking the armored equipment as the research object, this paper analyzes the task and demand of the operation process of relying on maintenance workshops to carry out equipment minor repairs in peacetime. The optimization goals are to minimize the total maintenance period and maximize the balance of maintenance personnel allocation, taking the professional and quantity requirements of maintenance personnel in the maintenance process as constraints, a mathematical model of the equipment minor repair operation process is constructed. And then aiming at the sequence relationship of maintenance procedures, a maintenance network process update algorithm with tabu table and a genetic algorithm considering equipment parallel maintenance operations are proposed to optimize the maintenance human resource allocation strategy for equipment minor maintenance operations. The example shows that the algorithm is reasonable and feasible.

Abstract Electroencephalography (EEG) is a non-invasive measurement method for brain activity. Due to its safety, high resolution, and hypersensitivity to dynamic changes in brain neural signals, EEG has aroused much interest in scientific research and medical fields. This article reviews the types of EEG signals, multiple EEG signal analysis methods, and the application of relevant methods in the neuroscience field and for diagnosing neurological diseases. First, three types of EEG signals, including time-invariant EEG, accurate event-related EEG, and random event-related EEG, are introduced. Second, five main directions for the methods of EEG analysis, including power spectrum analysis, time–frequency analysis, connectivity analysis, source localization methods, and machine learning methods, are described in the main section, along with different sub-methods and effect evaluations for solving the same problem. Finally, the application scenarios of different EEG analysis methods are emphasized, and the advantages and disadvantages of similar methods are distinguished. This article is expected to assist researchers in selecting suitable EEG analysis methods based on their research objectives, provide references for subsequent research, and summarize current issues and prospects for the future.

Abstract Focal and systemic infections are serious threats to human health. Preclinical models enable the development of new drugs and therapeutic regimens. In vivo, animal bioluminescence (BL) imaging has been used with bacterial reporter strains to evaluate antimicrobial treatment effects. However, high‐sensitivity bioluminescent systems are required because of the limited tissue penetration and low brightness of the BL signals of existing approaches. Here, we report that NanoLuc (Nluc) showed better performance than LuxCDABE in bacteria. However, the retention rate of plasmid constructs in bacteria was low. To construct stable Staphylococcus aureus reporter strains, a partner protein enolase (Eno) was identified by screening of S. aureus strain USA300 for fusion expression of Nluc‐based luciferases, including Nluc, Teluc, and Antares2. Different substrates, such as hydrofurimazine (HFZ), furimazine (FUR), and diphenylterazine (DTZ), were used to optimize a stable reporter strain/substrate pair for BL imaging. S. aureus USA300/Eno‐Antares2/HFZ produced the highest number of photons of orange‐red light in vitro and enabled sensitive BL tracking of S. aureus in vivo, with sensitivities of approximately 10 CFU from mouse skin and 750 CFU from mouse kidneys. USA300/Eno‐Antares2/HFZ was a powerful combination based on the longitudinal evaluation of the therapeutic efficacy of antibiotics. The optimized S. aureus Eno‐Antares2/HFZ pair provides a technological advancement for the in vivo evaluation of antimicrobial treatment.

Abstract Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.