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The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E. coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5, together facilitating tumor infiltration of adoptively transferred T cells. The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy. This combinatorial therapy, consisting of E. coli adjuvant and adoptive T-cell therapy, effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors. Notably, this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination. This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors, including melanoma and hepatocellular carcinoma, by converging attacks from both inside and outside the tumor tissues., Competing Interests: Competing interests: Z.G. is the co-founder of Zenomics Inc., ZCapsule Inc., and µZen Pharma Co., Ltd. The other authors declare no competing interests., (© 2024. The Author(s).)

Neurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The mud carp (Cirrhinus molitorella) is an important economic farmed fish, mainly distributed in South China and Southeast Asia due to its strong adaptability and high yield. Despite its economic importance, the paucity of genomic information has constrained detailed genetic research and breeding efforts. In this study, we utilized PacBio HiFi long-read sequencing and Hi-C technologies to generate a meticulously assembled chromosome-level genome of the mud carp. This assembly spans 1,033.41 Mb, with an impressive 99.82% distributed across 25 chromosomes. The contig N50 and scaffold N50 are 33.29 Mb and 39.86 Mb, respectively. The completeness of the mud carp genome assembly is highlighted by a BUSCO score of 98.05%. We predict 25,865 protein-coding genes, with a BUSCO score of 96.54%, and functional annotations for 91.83% of these genes. Approximately 52.21% of the genome consists of repeat elements. This high-fidelity genome assembly is a vital resource for advancing molecular breeding, comparative genomics, and evolutionary studies of the mud carp and related species., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Carya illinoinensis is an economically important nut tree, and its chloroplast (cp.) genome has been reported; however, its mitochondrial (mt) genome remains unknown. In the present study, we assembled the first mt genome of C. illinoinensis. The circular mt genome of C. illinoinensis is 495,205 bp long, with 37 protein-coding genes(PCGs), 24 tRNA genes, and 3 rRNA genes. All the tRNAs could be folded into typical cloverleaf secondary structures, with lengths of 58-88 bp. A conserved U-U-C-x-A-x2 consensus nucleotide sequence was discovered in the Ψ-loops of tRNA sequences. In addition, 447 dispersed repeats were detected, as well as found 482 RNA editing sites and 9,960 codons in the mt genome. Furthermore, a total of 27 DNA sequences with a length of 43,277 bp were transferred from the cp. to the mt genome, and eight integrated cp-derived genes (trnL-CAA, trnV-GAC, trnD-GUC, trnW-CCA, trnN-GUU, trnH-GUG, trnM-CAU, and rps7) were identified. We also obtained 1,086 hits, including 364.023 kp of nuclear genome sequences, that were transferred to the mt genome. To determine the evolutionary position of C. illinoinensis, we conducted a phylogenetic analysis of the mitogenomes of C. illinoinensis and 14 other taxa. The results strongly suggested that C. illinoinensis and Fagus sylvatica formed a single clade with 100% bootstrap support. This study sequenced comprehensive data on the C. illinoinensis mitochondrial genome and provided insights into the conserved sequences of tRNA genes, which could facilitate evolutionary research in other Carya trees in the future., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate The sampling of pecan cultivar Xinxuan-4 is not endangered in China, and no specific permission was required for the collection. The materials in this study were collected in the germplasm resource nursery of the Nanjing Botanical Garden with permission. Our experimental study complied with relevant institutional, national, and international guidelines and legislation. This article does not contain any studies with human participants or animals performed by any of the author., (© 2024. The Author(s).)

Hyperspectral imaging provides high-dimensional spatial-temporal-spectral information showing intrinsic matter characteristics 1-5 . Here we report an on-chip computational hyperspectral imaging framework with high spatial and temporal resolution. By integrating different broadband modulation materials on the image sensor chip, the target spectral information is non-uniformly and intrinsically coupled to each pixel with high light throughput. Using intelligent reconstruction algorithms, multi-channel images can be recovered from each frame, realizing real-time hyperspectral imaging. Following this framework, we fabricated a broadband visible-near-infrared (400-1,700 nm) hyperspectral image sensor using photolithography, with an average light throughput of 74.8% and 96 wavelength channels. The demonstrated resolution is 1,024 × 1,024 pixels at 124 fps. We demonstrated its wide applications, including chlorophyll and sugar quantification for intelligent agriculture, blood oxygen and water quality monitoring for human health, textile classification and apple bruise detection for industrial automation, and remote lunar detection for astronomy. The integrated hyperspectral image sensor weighs only tens of grams and can be assembled on various resource-limited platforms or equipped with off-the-shelf optical systems. The technique transforms the challenge of high-dimensional imaging from a high-cost manufacturing and cumbersome system to one that is solvable through on-chip compression and agile computation., (© 2024. The Author(s).)

A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (C min ) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid C min additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid C min , and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid C min had better predictive capability than that containing linezolid C min for predicting linezolid-induced thrombocytopenia in patients with renal impairment., (© 2024. The Author(s).)

Megachile is one of the largest bee genera, including nearly 1,500 species, but very few chromosome-level assemblies exist for this group or the family Megachilidae. Here, we report the chromosome-level genome assembly of Megachile lagopoda collected from Xizang, China. Using PacBio CLR long reads and Hi-C data, we assembled a genome of 256.83 Mb with 96.08% of the assembly located on 16 chromosomes. Our assembly contains 266 scaffolds, with a scaffold N50 length of 15.6 Mb, and BUSCO completeness of 99.20%. We masked 27.10% (69.61 Mb) of the assembly as repetitive elements, identified 459 non-coding RNAs, and predicted 11,157 protein-coding genes. This high-quality genome of M. lagopoda represents an important step forward for our knowledge of megachilid genomics and bee evolution overall., (© 2024. The Author(s).)

The aim of this study was to investigate the prevalence of diastasis recti abdominis (DRA) and to find the possible risk factors for DRA based on two diagnostic criteria among women in long-term postpartum period. A cross-sectional study was conducted on 1000 postpartum women at five different time points (3, 5, 10, 20, and 30 years after partum, respectively). Inter-recti distance (IRD) was assessed using ultrasound imaging, while basic data were collected through self-reported questionnaires. Two diagnostic criteria, IRD > 2 cm and IRD > 3 cm, were used to present the prevalence of DRA. Univariate and multivariate analyses were employed to explore the risk factors for DRA. When using the diagnostic criterion of IRD > 2 cm for DRA, the prevalence was 36%, 31%, 22%, 26%, and 30% at 3, 5, 10, 20, and 30 years postpartum, respectively. When using the diagnostic criterion of IRD > 3 cm for DRA, the prevalence was 13%, 8%, 6%, 8%, and 10%, respectively. The results revealed that higher body mass index (BMI) was a risk factor for DRA at 10 years postpartum (p = 0.000), bigger number of parturitions was a risk factor at 3, 5, and 10 years postpartum (p = 0.000, 0.004 and 0.000), twins was a risk factor at 3 years postpartum (p = 0.001), and diabetes was a risk factor at 20 and 30 years postpartum (P = 0.000 and 0.004). (1) The prevalence of DRA in the long-term postpartum period was high, especially when IRD > 2 cm was used as the diagnostic criterion. (2) Higher BMI, bigger number of parturitions, twins and diabetes were independently associated with higher odds of DRA at different long-term postpartum time points. (3) The diagnostic criterion for DRA should be further improved to avoid excessive clinical diagnosis and treatment. (1) This study elucidated the prevalence and risk factors associated with long-term postpartum DRA, thereby enhancing clinical awareness and advocating for early intervention and prevention measures to mitigate serious adverse outcomes. (2) This study presented the research results using two diagnostic criteria, increasing comparability with existing studies. In addition, discussions on reasonable diagnostic criterion for DRA were also conducted to avoid excessive clinical diagnosis and treatment., (© 2024. The Author(s).)

Extraction of gas from low-permeability thick coal seams poses challenges globally, attributed to low extraction efficiency, limited enrichment content, and extraction complexities. Investigating static fracturing in low-permeability thick coal seams holds substantial engineering significance and practical utility. This research delves into the current conditions in the Western region, characterized by low gas permeability and challenging extraction in thick coal seams. Through the utilization of FLAC 3D and COMSOL, simulation schemes are devised to analyze the influence of borehole parameters on fracture efficacy, elucidating the mechanisms by which external loads and internal gas pressure impact coal seam permeability. Field monitoring tests are employed to evaluate and model gas extraction enhancement via borehole positioning. The results suggest that the application of a static fracturing agent inducing 40 MPa expansion stress, along with a 75 mm borehole diameter and 0.5 m spacing, effectively fractures low-permeability thick coal seams. The spacing between extraction and fracturing holes adversely affects gas extraction efficiency due to the limited range of static fracturing. Field experiments demonstrate that static fracturing significantly improves gas extraction from low-permeability thick coal seams, resulting in a twofold increase in average gas extraction purity post-fracturing. This study establishes a robust theoretical foundation for optimizing gas extraction and mining activities in challenging low-permeability thick coal seam environments., (© 2024. The Author(s).)

Acute myeloid leukemia (AML) is a stem cell-driven malignancy of the blood forming (hematopoietic) system. Despite of high dose chemotherapy with toxic side effects, many patients eventually relapse. The "7+3 regimen", which consists of 7 days of cytarabine in combination with daunorubicin during the first 3 days, is a widely used therapy protocol. Since peripheral blood cells are easily accessible to longitudinal sampling, significant research efforts have been undertaken to characterize and reduce adverse effects on circulating blood cells. However, much less is known about the impact of the 7+3 regimen on human hematopoietic stem cells and their physiological micro-environments, the so-called stem cell niches. One reason for this is the technical inability to observe human stem cells in vivo and the discomfort related to bone marrow biopsies. To better understand the treatment effects on human stem cells, we consider a mechanistic mathematical model of the stem cell niche before, during and after chemotherapy. The model accounts for different maturation stages of leukemic and hematopoietic cells and considers key processes such as cell proliferation, self-renewal, differentiation and therapy-induced cell death. In the model, hematopoietic (HSCs) and leukemic stem cells (LSCs) compete for a joint niche and respond to both systemic and niche-derived signals. We relate the model to clinical trial data from literature which longitudinally quantifies the counts of hematopoietic stem like (CD34+CD38-ALDH+) cells at diagnosis and after therapy. The proposed model can capture the clinically observed interindividual heterogeneity and reproduce the non-monotonous dynamics of the hematopoietic stem like cells observed in relapsing patients. Our model allows to simulate different scenarios proposed in literature such as therapy-related impairment of the stem cell niche or niche-mediated resistance. Model simulations suggest that during the post-therapy phase a more than 10-fold increase of hematopoietic stem-like cell proliferation rates is required to recapitulate the measured cell dynamics in patients achieving complete remission. We fit the model to data of 7 individual patients and simulate variations of the treatment protocol. These simulations are in line with the clinical finding that G-CSF priming can improve the treatment outcome. Furthermore, our model suggests that a decline of HSC counts during remission might serve as an indication for salvage therapy in patients lacking MRD (minimal residual disease) markers., (© 2024. The Author(s).)

Methylmalonic acidemia (MMA) is the most common inborn organic acidemia, presenting multisystemic complications. Uric acid may have neurotoxic or neuroprotective effects due to its antioxidant or pro-inflammatory properties; however, its role in MMA brain injury remains unclear. We examined the correlation between the serum uric acid levels and brain imaging features of MMA. Data were collected from a cross-sectional study of 216 patients with MMA and 216 healthy matched controls aged 0-5 years in China. Serum uric acid levels were measured, and magnetic resonance imaging and computed tomography findings were retrieved from hospital records. Overall, 74.1% patients had brain abnormalities. Patients in the MMA group with abnormal brain imaging had higher serum uric acid levels than those in the MMA normal brain imaging and control groups. The area under the curve of serum uric acid was 0.74, 0.91, and 0.93 for MMA diagnosis with abnormal brain images, basal ganglia changes, and globus pallidus changes, respectively. Higher serum uric acid levels were independently associated with abnormal brain images. Children aged < 5 years with abnormal brain images in MMA exhibit elevated serum uric acid levels, serving as an effective auxiliary diagnostic indicator and independent risk factor for brain tissue injury., (© 2024. The Author(s).)

Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8 + T and CD4 + T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8 + T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management., (© 2024. The Author(s).)

The study aimed to assess the prospective associations between sleep duration, sleep restfulness, midday napping and hip fracture (HF) and falls in a nationally representative Chinese population. Data were from the China Health and Retirement Longitudinal Study which was conducted from 2013 to 2018. In total, 10,508 individuals without a history of HF in 2013 were included. Nighttime sleep duration, sleep restfulness and midday napping were self-reported. Logistic regression analyses were performed to examine the relationships between sleep problems and HF as well as falls, adjusting for covariates. A total of 313 (3.0%) participants reported HF, and 3899 (37.1%) experienced at least one fall event over the following 5-year period. Participants who had a short sleep duration (≤ 6) were more likely to report HF (OR = 1.27, 95% CI = 1.00-1.62) and falls (OR = 1.18, 95% CI = 1.07-1.30) than those who had a normal sleep duration (6-9 h) in the fully adjusted model. Participants having unrestful sleep were also more likely to report falls (OR = 1.23, 95% CI = 1.11-1.36) than those who had restful sleep. However, there was no significant association between midday napping and HF and falls. In conclusion, short sleep duration and sleep restfulness were independently associated with an increased risk of HF and falls, which may have important clinical and public health implications. Interventions to improve sleep quality may reduce the risk of HF and fall accidents among middle-aged and older people., (© 2024. The Author(s).)

Some studies have reported that the gut microbiota can influence adrenal-related hormone levels. However, the causal effects of the gut microbiota on adrenal function remain unknown. Therefore, we employed a two-sample Mendelian randomization (MR) study to systematically investigate the impact of gut microbiota on the function of different regions of the adrenal gland. The summary statistics for gut microbiota and adrenal-related hormones used in the two-sample MR analysis were derived from publicly available genome-wide association studies (GWAS). In the MR analysis, inverse variance weighting (IVW) was used as the primary method, with MR-Egger, weighted median, and cML-MA serving as supplementary methods for causal inference. Sensitivity analyses such as the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used to assess pleiotropy and heterogeneity. We identified 27 causal relationships between 23 gut microbiota and adrenal function using the IVW method. Among these, Sellimonas enhanced the function of the adrenal cortex reticularis zone (beta = 0.008, 95% CI: 0.002-0.013, P = 0.0057). The cML-MA method supported our estimate (beta = 0.009, 95% CI: 0.004-0.013, P = 2 × 10 - 4 ). Parasutterella, Sutterella, and Anaerofilum affect the functioning of different regions of the adrenal gland. Notably, pleiotropy was not observed. Our findings revealed that the gut microbiota is causally associated with adrenal function. This enhances our understanding of the gut-microbiota-brain axis and provides assistance in the early diagnosis and treatment of adrenal-related diseases in clinical practice., (© 2024. The Author(s).)

An issue that affects the scaling-up development of perovskite photovoltaics is the marked efficiency drop when enlarging the device area, caused by the inhomogeneous distribution of defected sites 1-3 . In the narrow band gap formamidinium lead iodide (FAPbI 3 ), the native impurities of PbI 2 and δ-FAPbI 3 non-perovskite could induce unfavoured non-radiative recombination, as well as inferior charge transport and extraction 4,5 . Here we develop an impurity-healing interface engineering strategy to address the issue in small-area solar cells and large-scale submodules. With the introduction of a functional cation, 2-(1-cyclohexenyl)ethyl ammonium, two-dimensional perovskite with high mobility is rationally constructed on FAPbI 3 to horizontally cover the film surface and to vertically penetrate the grain boundaries of three-dimensional perovskites. This unique configuration not only comprehensively transforms the PbI 2 and δ-FAPbI 3 impurities into stable two-dimensional perovskite and realizes uniform defect passivation but also provides interconnecting channels for efficient carrier transport. As a result, the FAPbI 3 -based small-area (0.085 cm 2 ) solar cells achieve a champion efficiency of more than 25.86% with a notably high fill factor of 86.16%. The fabricated submodules with an aperture area of 715.1 cm 2 obtain a certified record efficiency of 22.46% with a good fill factor of 81.21%, showcasing the feasibility and effectualness of the impurity-healing interface engineering for scaling-up promotion with well-preserved photovoltaic performance., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The prevalence of autism spectrum disorders (ASDs) differs substantially between males and females, suggesting that sex-related neurodevelopmental factors are central to ASD pathogenesis. Numerous studies have suggested that abnormal brain specialization patterns and poor regional cooperation contribute to ASD pathogenesis, but relatively little is known about the related sex differences. Therefore, this study examined sex differences in brain functional specialization and cooperation among children with ASD. The autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) derived from resting-state functional magnetic resonance imaging (rs-fMRI) were compared between 58 male and 13 female children with ASD. In addition, correlations were examined between regional CFH values showing significant sex differences and symptom scores on the autism behavior checklist (ABC) and childhood autism rating scale (CARS). Male children with ASD demonstrated significantly greater CFH in the left fusiform gyrus (FG) and right opercular part of the inferior frontal gyrus (IFGoperc) than female children with ASD. In addition, the CFH value of the left FG in male children with ASD was negatively correlated with total ABC score and subscale scores for sensory and social abilities. In contrast, no sex differences were detected in brain specialization. These regional abnormalities in interhemispheric cooperation among male children with ASD may provide clues to the neural mechanisms underlying sex differences in ASD symptomatology and prevalence. Autism spectrum disorders, sex, resting-state functional magnetic resonance imaging, cerebral specialization, interhemispheric cooperation., (© 2024. The Author(s).)

Deep learning-based defect detection methods have gained widespread application in industrial quality inspection. However, limitations such as insufficient sample sizes, low data utilization, and issues with accuracy and speed persist. This paper proposes a semi-supervised semantic segmentation framework that addresses these challenges through perturbation invariance at both the image and feature space. The framework employs diverse perturbation cross-pseudo-supervision to reduce dependency on extensive labeled datasets. Our lightweight method incorporates edge pixel-level semantic information and shallow feature fusion to enhance real-time performance and improve the accuracy of defect edge detection and small target segmentation in industrial inspection. Experimental results demonstrate that the proposed method outperforms the current state-of-the-art (SOTA) semi-supervised semantic segmentation methods across various industrial scenarios. Specifically, our method achieves a mean Intersection over Union (mIoU) 3.11% higher than the SOTA method on our dataset and 4.39% higher on the public KolektorSDD dataset. Additionally, our semantic segmentation network matches the speed of the fastest network, U-net, while achieving a mIoU 2.99% higher than DeepLabv3Plus., (© 2024. The Author(s).)

Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7-78.9%) and the DCR was 76% (95% CI: 54.9-90.6%). The mPFS was 6.0 months (95% CI: 5.4-9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response., (© 2024. The Author(s).)

Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL., (© 2024. The Author(s).)

The goal of our research is to elucidate and better assess placental function in rats with preeclampsia through an innovative application of ultrasound-based radiomics. Using a rat model induced with L-NAME, we carefully investigated placental dysfunction via microstructural analysis and immunoprotein level assessment. Employing the Boruta feature selection method on ultrasound images facilitated the identification of crucial features, consequently enabling the development of a robust model for classifying placental dysfunction. Our study included 12 pregnant rats, and thorough placental evaluations were conducted on 160 fetal rats. Distinct alterations in placental microstructure and angiogenic factor expression were evident in rats with preeclampsia. Leveraging high-throughput mining of quantitative image features, we extracted 558 radiomic features, which were subsequently used to construct an impressive evaluation model with an area under the receiver operating curve (AUC) of 0.95. This model also exhibited a remarkable sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 88.7%, 91.5%, 90.2%, 90.4%, and 90.0%, respectively. Our findings highlight the ability of ultrasound-based radiomics to detect abnormal placental features, demonstrating its potential for evaluating both normative and impaired placental function with high precision and reliability., (© 2024. The Author(s).)

Intermolecular distance largely determines the optoelectronic properties of organic matter. Conventional organic luminescent molecules are commonly used either as aggregates or as single molecules that are diluted in a foreigner matrix. They have garnered great research interest in recent decades for a variety of applications, including light-emitting diodes 1,2 , lasers 3-5 and quantum technologies 6,7 , among others 8-10 . However, there is still a knowledge gap on how these molecules behave between the aggregation and dilution states. Here we report an unprecedented phase of molecular aggregate that forms in a two-dimensional hybrid perovskite superlattice with a near-equilibrium distance, which we refer to as a single-molecule-like aggregate (SMA). By implementing two-dimensional superlattices, the organic emitters are held in proximity, but, surprisingly, remain electronically isolated, thereby resulting in a near-unity photoluminescence quantum yield, akin to that of single molecules. Moreover, the emitters within the perovskite superlattices demonstrate strong alignment and dense packing resembling aggregates, allowing for the observation of robust directional emission, substantially enhanced radiative recombination and efficient lasing. Molecular dynamics simulations together with single-crystal structure analysis emphasize the critical role of the internal rotational and vibrational degrees of freedom of the molecules in the two-dimensional lattice for creating the exclusive SMA phase. This two-dimensional superlattice unifies the paradoxical properties of single molecules and aggregates, thus offering exciting possibilities for advanced spectroscopic and photonic applications., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The rising carbon dioxide concentrations are expected to increase future rice yields. However, variations in the CO 2 fertilization effect (CFE) between rice subspecies and the influence of concurrent global warming introduce uncertainty in future global rice yield projections. Here we conducted a meta-analysis of rising carbon dioxide field experiments and employed crop modelling to assess future global rice yields for the top 14 rice producing countries. We found a robust parabolic relationship between rice CFE and temperature, with significant variations between rice subspecies. Our projections indicate that global rice production in the 2050s is expected to increase by 50.32 million tonnes (7.6%) due to CFE compared with historical production. Because low-income countries will experience higher temperatures, the gaps (difference of Δyield) between middle-to-high-income and low-income countries are projected to widen from the 2030s to the 2090s under elevated carbon dioxide. These findings underscore the critical role of CFE and emphasize the necessity to increase investments in research and technology for rice producing systems in low-income countries., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Postpancreatectomy hemorrhage (PPH) is an important risk factor for postoperative complications after laparoscopic pancreaticoduodenectomy (LPD). Recent studies have reported that the use of ligamentum teres hepatis (LTH) in LPD may reduce the risk of PPH. Therefore, this study aims to investigate whether wrapping the hepatic hilar artery with the LTH can reduce PPH after LPD. We reviewed the data of 131 patients who underwent LPD in our team from April 2018 to December 2023. The patients were divided into Groups A (60 patients) and B (71 patients) according to whether the hepatic portal artery was wrapped or not. The perioperative data of the two groups were compared to evaluate the effect of LTH wrapping the hepatic hilar artery on LPD. The platelet count of Group A was (225.25 ± 87.61) × 10^9/L, and that of Group B was (289.38 ± 127.35) × 10^9/L, with a statistically significant difference (p < 0.001). The operation time of group A [300.00 (270.00, 364.00)] minutes was shorter than that of group B [330.00 (300.00, 360.00)] minutes, p = 0.037. In addition, A set of postoperative hospital stay [12.00 (10.00, 15.00)] days shorter than group B [15.00 (12.00, 19.50)] days, p < 0.001. No PPH occurred in Group A, while 8 patients in Group B had PPH (7 cases of gastroduodenal artery hemorrhage and 1 case of proper hepatic artery hemorrhage), p = 0.019. The new technique of wrapping the hepatic hilar artery through the LTH can effectively reduce the occurrence of PPH after LPD., (© 2024. The Author(s).)

Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS&#95;SIGNALING&#95;UP pathway in AR and related to HYPOXIA, TGF&#95;BETA&#95;SIGNALING and TNFA&#95;SIGNALING&#95;VIA&#95;NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE., (© 2024. The Author(s).)

In this paper, a novel Moth-Flame Optimization (MFO) algorithm, namely MFO algorithm enhanced by Multiple Improvement Strategies (MISMFO) is proposed for solving parameter optimization in Multi-Kernel Support Vector Regressor (MKSVR), and the MISMFO-MKSVR model is further employed to deal with the software effort estimation problems. In MISMFO, the logistic chaotic mapping is applied to increase initial population diversity, while the mutation and flame number phased reduction mechanisms are carried out to improve the search efficiency, as well the adaptive weight adjustment mechanism is used to accelerate convergence and balance exploration and exploitation. The MISMFO model is verified on fifteen benchmark functions and CEC 2020 test set. The results show that the MISMFO has advantages over other meta-heuristic algorithms and MFO variants in terms of convergence speed and accuracy. Additionally, the MISMFO-MKSVR model is tested by simulations on five software effort datasets and the results demonstrate that the proposed model has better performance in software effort estimation problem. The Matlab code of MISMFO can be found at https://github.com/loadstar1997/MISMFO ., (© 2024. The Author(s).)

Accurate prediction of regional terrestrial water storage change (TWSA) is of great significance for water resources planning and management, and early warning of extreme climate disasters. Aiming at the problem that the conventional methods on prediction of TWSA time series are difficult to be accurate, the six typical regions are selected in China as examples, including the upper reaches of the Yangtze River (UYR), the southwest region (SWR), the Liaohe River Basin (LRB), the North China Plain (NCP), the Qinghai-Tibet Plateau (QTP), and the Pearl River Basin (PRB). The mascon product from GRACE/GRACE-FO provided by CSR is used to extract TWSA time series in six typical areas. The improved Back Propagation (BP) neural network, Long Short-Term Memory (LSTM) neural network and the latest Bidirectional LSTM (BiLSTM-attention) neural network model based on attention mechanism are proposed to predict and analyze the regional TWSA. In the experiment, the selection of the optimal model parameters such as the number of hidden layer nodes and the number of hidden units of the neural network model is tested and analyzed in detail. Meanwhile, the model prediction results are compared with the traditional least squares method and random forest (RF) prediction method. The root mean square error (RMSE), determination coefficient (R 2 ), Nash-Sutcliffe efficiency coefficient (NSE) and mean absolute percentage error (MAPE) were used to evaluate the accuracy of the predicted results. The results show that the improved BP, LSTM and Bi-LSTM-attention neural network models all achieve higher prediction accuracy in UYR and SWR areas. RMSE is less than 2.641 cm, R 2 is as high as 0.8 or more, NSE is above 0.6, and MAPE is within 0.1. Compared with the least square method, the RMSE of the predicted results from three neural network decreased by 0.998 cm, 0.700 cm and 0.7563 on average, and the R 2 increased by 81.75%, 69.89% and 72% on average. Compared with RFML method, the RMSE from three neural network is reduced by 0.601 cm, 0.316 cm and 0.360, and R 2 is increased by 38.20%, 24.60% and 27.06% on average. NSE and RMSE are improved to varying degrees in the above regions. It shows that the improved BP, LSTM and BiLSTM-attention model used can effectively predict TWSA. The research methods and results in this paper can provide important reference for the rational utilization of regional water resources and disaster risk assessment., (© 2024. The Author(s).)

The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds., (© 2024. The Author(s).)

In this article, a visual security image encryption algorithm based on compressed sensing is proposed. The algorithm consists of two stages: the compression and encryption stage and the embedding stage. The key streams in the compression and encryption stage are generated by a newly constructed four-dimensional discrete chaotic map, while the Gaussian measurement matrix is generated by a Chebyshev map, and both of their generations are related to the feature code of the carrier image, which enhances the security of the ciphertext. In the compression and encryption stage, a scrambling-cyclic shift-diffusion encryption structure is adopted for the compressed image in which the shift number in the cyclic shift stage and the diffusion key streams are dynamically changed according to each pixel value, so the algorithm can resist chosen plaintext attack. In the embedding stage, the carrier image is first subjected to integer wavelet transform to obtain the high-frequency and low-frequency components of the image, and then the intermediate ciphertext information is embedded into its high-frequency components. Finally, the carrier image is subjected to inverse integer wavelet transform to obtain a visually secure ciphertext image. The experimental results and security analysis indicate that the encryption scheme has a large key space, high decryption key sensitivity, similar histogram distribution between the carrier image and the visual security ciphertext image, and good robustness to noise attacks., (© 2024. The Author(s).)

Hyperuricemia (HUA), a metabolic disease caused by excessive production or decreased excretion of uric acid (UA), has been reported to be closely associated with a variety of UA transporters. Clerodendranthus spicatus (C. spicatus) is an herbal widely used in China for the treatment of HUA. However, the mechanism has not been clarified. Here, the rat model of HUA was induced via 10% fructose. The levels of biochemical indicators, including UA, xanthine oxidase (XOD), adenosine deaminase (ADA), blood urea nitrogen (BUN), and creatinine (Cre), were measured. Western blotting was applied to explore its effect on renal UA transporters, such as urate transporter1 (URAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette super-family G member 2 (ABCG2). Furthermore, the effect of C. spicatus on plasma metabolites was identified by metabolomics. Our results showed that C. spicatus could significantly reduce the serum levels of UA, XOD, ADA and Cre, and improve the renal pathological changes in HUA rats. Meanwhile, C. spicatus significantly inhibited the expression of URAT1 and GLUT9, while increased the expression of ABCG2 in a dose-dependent manner. Metabolomics showed that 13 components, including 1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-PE, Tyr-Leu and N-cis-15-Tetracosenoyl-C18-sphingosine, were identified as potential biomarkers for the UA-lowering effect of C. spicatus. In addition, pathway enrichment analysis revealed that arginine biosynthesis, biosynthesis of amino acids, pyrimidine metabolism and other metabolic pathways might be involved in the protection of C. spicatus against HUA. This study is the first to explore the mechanism of anti-HUA of C. spicatus through molecular biology and metabolomics analysis, which provides new ideas for the treatment of HUA., (© 2024. The Author(s).)

The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically 1,2 . This results in substantial accumulation of lacate, the end product of anaerobic glycolysis, in cancer cells 3 . However, how cancer metabolism affects chemotherapy response and DNA repair in general remains incompletely understood. Here we report that lactate-driven lactylation of NBS1 promotes homologous recombination (HR)-mediated DNA repair. Lactylation of NBS1 at lysine 388 (K388) is essential for MRE11-RAD50-NBS1 (MRN) complex formation and the accumulation of HR repair proteins at the sites of DNA double-strand breaks. Furthermore, we identify TIP60 as the NBS1 lysine lactyltransferase and the 'writer' of NBS1 K388 lactylation, and HDAC3 as the NBS1 de-lactylase. High levels of NBS1 K388 lactylation predict poor patient outcome of neoadjuvant chemotherapy, and lactate reduction using either genetic depletion of lactate dehydrogenase A (LDHA) or stiripentol, a lactate dehydrogenase A inhibitor used clinically for anti-epileptic treatment, inhibited NBS1 K388 lactylation, decreased DNA repair efficacy and overcame resistance to chemotherapy. In summary, our work identifies NBS1 lactylation as a critical mechanism for genome stability that contributes to chemotherapy resistance and identifies inhibition of lactate production as a promising therapeutic cancer strategy., (© 2024. The Author(s).)

The greater amberjack is a very important fishery species with high commercial value, and it is distributed worldwide. Transcriptome-based studies on S. dumerili have been limited by an inadequate reference genome and a lack of well-annotated full-length transcripts. In this study, a total of 12 tissues from juvenile and adult fish both sexes were collected for next-generation RNA sequencing (RNA-seq) and full-length isoform sequencing (Iso-seq). For Iso-seq, a total of 163,218, 149,716, and 189,169 high-quality unique transcript sequences were obtained, with an N50 of 5,441, 5,255, and 5,939, from juvenile, adult male and adult female S. dumerili, respectively. We integrated the Iso-seq and RNA-seq data to construct a comprehensive gene annotation and systematically profiled the dynamics of gene expression across the 12 tissues. Our gene models had greater detail and accuracy than those from NCBI and Ensembl, with more precise polyA locations. These resources serve as a foundation for functional genomic studies and provide valuable insights into the molecular mechanisms underlying the development, reproduction and commercial traits of amberjack., (© 2024. The Author(s).)

The striated frogfish (Antennarius striatus), a member of the sub-order Antennarioidei within the order Lophiiformes, possesses remarkable adaptations. These include the ability to modulate body coloration for camouflage, utilize bioluminescent esca for predation, and employ elbow-like pectoral fins for terrestrial locomotion, making it a valuable model for studying bioluminescence, adaptive camouflage, fin-to-limb transition, and walking-like behaviors. To better study and contribute to the conservation of the striated frogfish, we obtained the micro-CT image of the pectoral fin bones and generated a high-quality, chromosome-level genome assembly using multiple sequencing technologies. The assembly spans 548.56 Mb with a contig N50 of 21.05 Mb, and 99.35% of the genome is anchored on 24 chromosomes, making it the most complete genome available within Lophiiformes. The genome annotation revealed 28.43% repetitive sequences and 23,945 protein-coding genes. This chromosome-level genome provides valuable genetic resources for frogfish conservation and offers insights into the genetic mechanisms underlying its unique phenotypic evolution. Furthermore, it establishes a foundation for future research on limb development and adaptive camouflage in this species., (© 2024. The Author(s).)

Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC., (© 2024. The Author(s).)

Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser 780 to Pro 810 . Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca 2+ release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat., (© 2024. The Author(s).)

Mayo Imaging Classification (MIC) for predicting future kidney growth in autosomal dominant polycystic kidney disease (ADPKD) patients is calculated from a single MRI/CT scan assuming exponential kidney volume growth and height-adjusted total kidney volume at birth to be 150 mL/m. However, when multiple scans are available, how this information should be combined to improve prediction accuracy is unclear. Herein, we studied ADPKD subjects ( n = 36 ) with 8+ years imaging follow-up (mean = 11 years) to establish ground truth kidney growth trajectory. MIC annual kidney growth rate predictions were compared to ground truth as well as 1- and 2-parameter least squares fitting. The annualized mean absolute error in MIC for predicting total kidney volume growth rate was 2.1 % ± 2 % compared to 1.1 % ± 1 % ( p = 0.002 ) for a 2-parameter fit to the same exponential growth curve used for MIC when 4 measurements were available or 1.4 % ± 1 % ( p = 0.01 ) with 3 measurements averaging together with MIC. On univariate analysis, male sex ( p = 0.05 ) and PKD2 mutation ( p = 0.04 ) were associated with poorer MIC performance. In ADPKD patients with 3 or more CT/MRI scans, 2-parameter least squares fitting predicted kidney volume growth rate better than MIC, especially in males and with PKD2 mutations where MIC was less accurate., (© 2024. The Author(s).)

In order to investigate the acoustic oscillation characteristics of gas-liquid pintle rocket engines and elucidate the path by which spray combustion process provides energy to the combustor pressure oscillation, a LOX/GCH 4 pintle engine with rectangular combustor was designed. By adding transverse velocity disturbance for the first time, the acoustic response of spray combustion process was simulated, and the effect of excitation amplitude on acoustic response was researched. Numerical results show that the adopted transverse velocity disturbance can excite the first-order transverse acoustic oscillation with same excitation frequency in the engine combustor. The acoustic response maintenance mechanism under extrinsic excitation is summarized for pintle engines. Besides, the temperature distribution inside the engine combustor tends to be uniform, and the low-frequency oscillation caused by the flame transverse swing gradually disappears. The amplitude of combustor pressure oscillation is dominated by excitement amplitude and phase difference between the pressure and heat release in combustion reaction region. In addition, the time-averaged combustor pressure can be amplified mainly by transverse velocity disturbance. The research work can provide a reference for related fire tests on the acoustic response of a subscale gas-liquid pintle engine., (© 2024. The Author(s).)

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen., (© 2024. The Author(s).)

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It's essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV., (© 2024. The Author(s).)

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In order to protect intangible cultural heritage and promote outstanding cultural works, this article introduces innovative research on Shen Embroidery using convolutional neural networks. The dataset of Shen Embroidery was preprocessed to augment the data required for experimentation. Moreover, the approach of transfer learning was introduced to fine-tune the recognition network. Specifically, Spatial Pyramid Pooling (SPP) is employed by replacing the avg pool in the MobileNet V1 network, achieving the fusion of local and global features. The experimental results showed that the improved MobileNet V1 achieved a recognition accuracy of 98.45%, which was 2.3% higher than the baseline MobileNet V1 network. The experiments demonstrated that the improved convolutional neural network can efficiently recognize Shen Embroidery and provide technical support for the intelligent development of intangible cultural heritage., (© 2024. The Author(s).)

E-beam lithography is a powerful tool for generating nanostructures and fabricating nanodevices with fine features approaching a few nanometers in size. However, alternative approaches to conventional spin coating and development processes are required to optimize the lithography procedure on irregular surfaces. In this review, we summarize the state of the art in nanofabrication on irregular substrates using e-beam lithography. To overcome these challenges, unconventional methods have been developed. For instance, polymeric and nonpolymeric materials can be sprayed or evaporated to form uniform layers of electron-sensitive materials on irregular substrates. Moreover, chemical bonds can be applied to help form polymer brushes or self-assembled monolayers on these surfaces. In addition, thermal oxides can serve as resists, as the etching rate in solution changes after e-beam exposure. Furthermore, e-beam lithography tools can be combined with cryostages, evaporation systems, and metal deposition chambers for sample development and lift-off while maintaining low temperatures. Metallic nanopyramids can be fabricated on an AFM tip by utilizing ice as a positive resistor. Additionally, Ti/Au caps can be patterned around a carbon nanotube. Moreover, 3D nanostructures can be formed on irregular surfaces by exposing layers of anisole on organic ice surfaces with a focused e-beam. These advances in e-beam lithography on irregular substrates, including uniform film coating, instrumentation improvement, and new pattern transferring method development, substantially extend its capabilities in the fabrication and application of nanoscale structures., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2024.)

The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors., (© 2024. The Author(s).)

The pig-nosed turtle (Carettochelys insculpta) represents the only extant species within the Carettochelyidae family, is a unique Trionychia member fully adapted to aquatic life and currently facing endangerment. To enhance our understanding of this species and contribute to its conservation efforts, we employed high-fidelity (HiFi) and Hi-C sequencing technology to generate its genome assembly at the chromosome level. The assembly result spans 2.18 Gb, with a contig N50 of 126 Mb, encompassing 34 chromosomes that account for 99.6% of the genome. The assembly has a BUSCO score above 95% with different databases and strong collinearity with Yangtze giant softshell turtles (Rafetus swinhoei), indicating its completeness and continuity. A total of 19,175 genes and 46.86% repetitive sequences were annotated. The availability of this chromosome-scale genome represents a valuable resource for the pig-nosed turtle, providing insights into its aquatic adaptation and serving as a foundation for future turtle research., (© 2024. The Author(s).)

The construction of super large section (SLS) shallow buried tunnels involves challenges related to their large span, high flat rate, and complex construction process. Selecting an appropriate excavation method is crucial for ensuring stability, controlling costs, and managing the construction timeline. This study focuses on the selection of excavation methods and the mechanical responses of SLS tunnels in different types of surrounding rock. The research is based on the Yangjiashan tunnel project in Zhejiang Province, China, which is a four-line highway tunnel with a span of 21.3 m. Three sequential excavation methods were proposed and simulated using the three-dimensional finite difference method: the "upper first and lower later" side drift (SD) method, the central diaphragm method, and the top heading and bench (HB) method. The mechanical response characteristics of tunnel construction under these methods were investigated, including rock deformation, rock pressure, and the internal forces acting on the primary support. By comparing the performance of the three construction methods in rock masses of Grades III to V, the study aimed to determine the optimal construction method for SLS tunnels considering factors such as safety, cost, and schedule. Field tests were conducted to evaluate the effectiveness of the optimized construction scheme. The results of the field monitoring indicated that the "upper first and lower later" SD method in Grade V rock mass and the HB method in Grade III to IV rock mass are feasible and cost-effective under certain conditions. The research findings provide valuable insights for the design and construction of SLS tunnels in complex conditions, serving as a reference for engineers and project managers., (© 2024. The Author(s).)

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing., (© 2024. The Author(s).)

Monitoring and predicting the regional groundwater storage (GWS) fluctuation is an essential support for effectively managing water resources. Therefore, taking Shandong Province as an example, the data from Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-On (GRACE-FO) is used to invert GWS fluctuation from January 2003 to December 2022 together with Watergap Global Hydrological Model (WGHM), in-situ groundwater volume and level data. The spatio-temporal characteristics are decomposed using Independent Components Analysis (ICA), and the impact factors, such as precipitation and human activities, which are also analyzed. To predict the short-time changes of GWS, the Support Vector Machines (SVM) is adopted together with three commonly used methods Long Short-Term Memory (LSTM), Singular Spectrum Analysis (SSA), Auto-Regressive Moving Average Model (ARMA), as the comparison. The results show that: (1) The loss intensity of western GWS is significantly greater than those in coastal areas. From 2003 to 2006, GWS increased sharply; during 2007 to 2014, there exists a loss rate - 5.80 ± 2.28 mm/a of GWS; the linear trend of GWS change is - 5.39 ± 3.65 mm/a from 2015 to 2022, may be mainly due to the effect of South-to-North Water Diversion Project. The correlation coefficient between GRACE and WGHM is 0.67, which is consistent with in-situ groundwater volume and level. (2) The GWS has higher positive correlation with monthly Global Precipitation Climatology Project (GPCP) considering time delay after moving average, which has the similar energy spectrum depending on Continuous Wavelet Transform (CWT) method. In addition, the influencing facotrs on annual GWS fluctuation are analyzed, the correlation coefficient between GWS and in-situ data including the consumption of groundwater mining, farmland irrigation is 0.80, 0.71, respectively. (3) For the GWS prediction, SVM method is adopted to analyze, three training samples with 180, 204 and 228 months are established with the goodness-of-fit all higher than 0.97. The correlation coefficients are 0.56, 0.75, 0.68; RMSE is 5.26, 4.42, 5.65 mm; NSE is 0.28, 0.43, 0.36, respectively. The performance of SVM model is better than the other methods for the short-term prediction., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

To reduce the adverse impact of demolition of the symmetrical rigid frame arch bridge overcrossing the highway with over-saturated traffic flow, a rapid demolition method based on the Self-Propelled Modular Transporter (SPMT) technique was developed in this study. The calculation formulae for reaction forces of the supporting brackets, as well as driving force and stability of SPMTs, were derived by analyzing the stability, synchronization, and influencing parameters of the cut bridge body-transport system. In addition, a monitoring system during the whole process was developed to ensure the demolition safety. An application of demolishing a crossline symmetrical rigid frame arch bridge in China within 5 h has been presented. The results showed that the proposed method can be successfully applied in real projects, leading to significant reduction in traffic impact, energy consumption, and environmental pollution., (© 2024. The Author(s).)