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The spider genus Xizangiana Sherwood, Li & Zhang, 2022, comprises nine species that inhabit northern India and south-western China. Six of these species have been documented in the Xizang Autonomous Region of China.A new species, Xizangiana plankton sp. nov. is described and illustrated from Xizang Autonomous Region, China.

Moringa oleifera is a perennial medicinal and edible plant, and polyphenols as one of its main active ingredients. This study reviews the current status of development of the polyphenol types and contents of different parts, polyphenol extraction methods, polyphenol efficacy, and polyphenol applications of Moringa oleifera. Additionally, the current research on the antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, and hypoglycemic properties of polyphenols from Moringa oleifera is critically examined. The aim of this review is to provide a theoretical basis as well as new insights into the future research and applications of Moringa oleifera polyphenols.

Previous studies have confirmed that intervertebral disc degeneration (IDD) is closely associated with inflammation-induced reactive oxygen species (ROS) and resultant cell mitochondrial membrane potential (MMP) decline. Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline. Additionally, re-energizing the mitochondria damaged in the inflammatory milieu to restore their function, is equally important. Herein, we proposed an interesting concept of mitochondrion-engine equipped with coolant, which enables first to “cool-down” the inflammatory environment, next to restore the MMP, finally to allow cells to regain normal energy metabolism through materials design. As such, we developed a multi-functional composite composed of a reactive oxygen species (ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane (TPU) scaffold. The TPU scaffold was coated with conductive polypyrrole (PPy) to electrophoretically deposit l-arginine, which could upregulate the Mammalian target of rapamycin (mTOR) pathway, thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair. While the ROS-responsive hydrogel acting as the “mito-engine coolant” could scavenge the excessive ROS to create a favorable environment for IVD cells recovery. Demonstrated by in vitro and in vivo evaluations, the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress. Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair. This unique bioinspired design integrated biomaterial science with mitochondrial biology, presents a promising paradigm for IDD treatment.

Lithium element enrichment is widely observed in the coal-bearing series of the Late Permian Heshan Formation in Shanglin, Guangxi, which has potential economic value and research significance. In this study, a multi-proxy study was conducted for evaluating major elements, trace elements, zircon U–Pb dating, and zircon trace elements from the lithium mineralization layers to characterize the spatial distribution, elemental geochemical characteristics, and provenance of lithium mineralization layers of the Late Permian Heshan Formation coal-bearing series in the Wanfu mining area, Shanglin, Guangxi. Thirty four samples were selected from lithium mineralization layers in order to determine major elements and trace elements. Moreover, the zircon U–Pb dating and zircon trace elements of one sample was investigated. The study reveals that four sets of lithium mineralization layers, namely I, II, III, and IV, are developed from bottom to top in the Heshan Formation coal-bearing series from the Wanfu mining area, Shanglin, Guangxi. According to the order of lithium content from high to low, it is divided into lithium mineralization layers I, III, II and IV. Compared with average values for world claystone, the lithium mineralization layer I are highly enriched in Li, the II and III is enriched in Li, and the IV is slightly enriched in Li. The analysis of Al2O3–TiO2, La/Sc-Th/Co and V–Ni–Th×10 diagrams indicate that most of the samples of lithium mineralization layer I, III and IV fall close to the acidic volcanic rocks field, while a few samples of lithium mineralization layer I fall near the intermediate volcanic rocks field. Therefore, it is inferred that the lithium mineralization layers of the Heshan Formation in Shanglin, Guangxi are dominated by sediments derived from the acidic and intermediate volcanic rocks. The Zircon U–Pb dating, Th/Nb-Hf/Th and Th/U–Nb/Hf tectonic setting discrimination diagrams of zircon trace elements, rare earth elements analysis, and Al2O3–TiO2, La/Sc−Th/Co, V–Ni–Th×10 and Nb/Y–Zr/TiO2 source rock discrimination diagrams indicate that the lithium mineralization layers of the Heshan Formation coal-bearing series in the Wanfu mining area mainly come from acidic and intermediate volcanic rocks related to the Emeishan Igneous Province and the Paleo-Tethys Permian magmatic arc.

[Introduction] The rapid development of new energy vehicles (NEVs) brings higher requirements for the power demand of highways. Based on the analysis of the power loads of highways, the photovoltaic endowment, and the energy storage technologies suitable for highway service areas in China, this paper explores the self-consistency of the highway transportation and energy integration mode of the PV-Storage-Charging integrated development path, and combines practical engineering project to demonstrate and analyze the feasibility of the highway transportation and energy integration mode. [Method] By analyzing the total mileage of highways in China, the market penetration rate of NEVs, and the PV & energy storage resources of highway transportation, based on the potential increase in highway power load due to the growth of NEVs and the utilization space of photovoltaic resources in highway transportation, a comprehensive energy utilization mode of PV-Storage-Charging for highway service areas was proposed. Combined with existing projects of self-consistent modes of transportation and energy integration, suggestions were proposed for the integrated development mode of highway PV-Storage-Charging. [Result] Data indicates that by 2025, the national stock of NEVs will exceed 25 million, consuming 37.5 TWh of electricity, showing tremendous potential for electricity demand. At the same time, the abundant photovoltaic resources along and around roads in China have a photovoltaic generation potential of approximately 1022.8 TW, while the calculated annual energy consumption of highway infrastructure is approximately 17.99 TW. [Conclusion] The main path of integration between transportation and energy should start with developing wind and photovoltaic natural resource endowments based on the infrastructure of road transportation itself, and forming a self-consistent supply of transportation energy systems, thereby constructing a distributed, green, renewable, and net zero-emission energy supply system for transportation systems. The integrated development path of PV-Storage-Charging transportation and energy integration can consume renewable energy locally, alleviate grid pressure while promoting the clean energy utilization of highways, showing immense potential. This paper can provide theoretical support and reference for the development of highway transportation and energy integration in China.

Abstract This study addresses the distribution and antimicrobial resistance of Acinetobacter baumannii (A. baumannii) in a medical facility in Haikou City, aiming to provide essential insights for enhancing in-hospital treatment and prevention strategies. We conducted a retrospective analysis of 513 A. baumannii isolates collected from a tertiary care hospital in Haikou between January 2018 and December 2020, focusing on their antimicrobial resistance patterns. Random Amplified Polymorphic DNA (RAPD) analysis was performed on 48 randomly selected A. baumannii strains. Using Gel-pro4.0 and NTSYSspc2.10 software, we constructed dendrograms to assess the genetic diversity of these strains. Our results indicate that males between 60 and 70 years old are particularly vulnerable to A. baumannii infections, which are most frequently detected in sputum samples, with a detection rate exceeding 70%. Alarmingly, over 50% of the isolates were identified as multi-drug resistant. The RAPD-PCR fingerprinting cluster analysis demonstrated substantial genetic diversity among the strains. Using primer OPA-02 at a 45% similarity coefficient, the strains were categorized into four groups (A-D), with group A being predominant (39 strains). high-prevalence areas like the Neurosurgery and Intensive Care Medicine Wards require enhanced surveillance and targeted interventions to manage Group C infections effectively. Additionally, the varied presence of other groups necessitates customized strategies to address the specific risks in each ward. Similarly, primer 270 at a 52% similarity coefficient classified the strains into five groups (E-I), with group E being most common (36 strains). The study highlights a concerning prevalence of antimicrobial resistance, particularly multi-drug resistance, among A. baumannii strains in the Haikou hospital. The significant genetic diversity, especially within groups A and E, underscores the need for tailored hospital treatment protocols and prevention measures. These findings contribute to the growing body of research on antimicrobial resistance, emphasizing the urgent need for effective management strategies in healthcare settings.

Abstract Conventional magnetic biosensing technologies have reduced analytical capacity for magnetic field dimensionality and require extensive sample processing. To address these challenges, we spatially engineer 3D magnetic response gradients for direct and programmable molecular detection in native biofluids. Named magnetic augmentation through triple-gradient coupling for high-performance detection (MATCH), the technology comprises gradient-distributed magnetic nanoparticles encapsulated within responsive hydrogel pillars and suspended above a magnetic sensor array. This configuration enables multi-gradient matching to achieve optimal magnetic activation, response and transduction, respectively. Through focused activation by target biomarkers, the platform preferentially releases sensor-proximal nanoparticles, generating response gradients that complement the sensor’s intrinsic detection capability. By implementing an upstream module that recognizes different biomarkers and releases universal activation molecules, the technology achieves programmable detection of various circulating biomarkers in native plasma. It bypasses conventional magnetic labeling, completes in

Abstract Background Lipids and thyroid hormones (TH) are closely interrelated. However, previous studies have not mentioned the linkage encompassing the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) alongside TH level, as well as sensitivity indices. Methods This cross-sectional study leverages expansive datasets from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. Weighted multivariate linear regression, smoothed curve fitting and sensitivity analyses were used to investigate the associations of the NHHR with the thyroid. Subgroup analyses and interaction tests were conducted to determine the robustness of the findings across diverse segments of the population, ensuring the consistency and generalizability of the observed associations. Results The NHHR was significantly positively correlated with free triiodothyronine (FT3) levels, thyroid-stimulating hormone (TSH) levels, the FT3 to FT4 ratio (FT3/FT4), and the quantile-based thyroid feedback index for FT3 (TFQIFT3) and negatively correlated with free thyroxin (FT4) levels [0.17(0.07–0.27), P = 0.001; 0.60 (0.03–1.17), P = 0.040; 0.06 (0.04–0.08), P

Abstract There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.

Abstract Background Mushroom poisoning is a significant food safety issue in Guizhou Province, China. Studies on this topic are essential for its prevention and control. We aimed to analyze the epidemiological characteristics of mushroom poisoning and study the correlation between its cases and meteorological factors in Guizhou Province. Methods We collected data on mushroom poisoning and meteorological factors in Guizhou Province in 2023. A descriptive analysis was conducted on the epidemiological features of mushroom poisoning and meteorological factors. We used Spearman correlation analysis and the generalized additive model to examine the relationship between meteorological factors and the number of mushroom poisoning cases. Results In 2023, mushroom poisoning cases in Guizhou Province were concentrated among individuals aged 20–59. Clinical symptoms were primarily gastrointestinal symptoms and occurrences peaked from June to October, mainly in the northeastern region of the province. Most incidents occurred in households. In 72 mushroom poisoning incidents where species were identified, 33 poisonous mushrooms were found. The number of mushroom poisoning cases in Guizhou Province was positively correlated with each meteorological factor(P

Objectives: This study aimed to survey the geriatric nursing competencies of clinical nursing staff in Chongqing City, China, and provide suggestions to enhance these competencies. Methods: This study was conducted in 204 hospitals in Southwest China from December 24, 2022 to January 7, 2023. The “Geriatric Nursing Competence of Clinical Nurse Investigation Tool” was used to explore factors that influence geriatric nurses’ competencies via stratified sampling. The survey was conducted by distributing and collecting questionnaires through the online platform Wenjuanxing. Results: A total of 10,692 nurses answered the questionnaires. Of these questionnaires, 9,442 were valid. The total geriatric nursing competence score of the clinical nursing staff was 2.29 ± 0.81, the secondary hospital score was 2.23 ± 0.78, and the tertiary hospital’s overall mean score was 2.33 ± 0.83. The factors that influenced secondary hospitals included the department of medicine, age of nurses and total length of career (P

Abstract Background Total knee arthroplasty (TKA) successfully alleviates pain from knee osteoarthritis, but muscle strength and function are reduced for a long period postoperatively. Postoperative active resistance exercise may play a relevant role. Purpose To systematically evaluate effects of lower-limb active resistance exercise (ARE) on mobility, physical function, muscle strength and pain intensity in patients with TKA. Methods A search was conducted in PubMed, EMBASE, and Cochrane Library databases from inception to September 2023. Only randomized controlled trials (RCTs) that compared the effects of ARE and no intervention or other rehabilitation program without PRE were included. The outcome variables were mobility (Maximal walking speed [MWS]/6-Minute Walk Test[6MWT]), physical function (Stair Climb Test [SCT]/Timed Up and Go [TUG]), knee extension/ flexion power(KEP/KFP), joint range of motion (ROM) and pain. Standardized Mean Differences (SMD) or Mean Differences (MD) and 95% confidence intervals (CI) were calculated and combined in meta-analyses. The Cochrane Collaboration’s Handbook were used for the methodological quality assessments. GRADE was used to assess the quality of evidence. The meta-analysis was performed using the RevMan 5.4 software. Results A total of 14 randomized controlled trials, involving 880 patients, were finally included. The lower-limb ARE exhibited significantly greater improvement in MWS (MD 0.13, 95%CI 0.08–0.18, P

Abstract Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

Abstract Background The commercial utilization of genetically modified soybeans has yielded substantial economic advantages. Nevertheless, the genetic drift towards wild soybeans is one of the main ecological risks that needs to be addressed. Previous experiments demonstrated the absence of fitness cost or florescence overlap in hybrid offspring resulting from the crossbreeding of transgenic soybean GTS40-3-2 and Zhengzhou wild soybeans. In this study, hybrid progeny was systematically crossed with wild soybeans to establish a backcross progeny system. This system was employed to evaluate the ecological risk associated with the backcross progeny of transgenic and wild soybeans. Results The findings indicated that the offspring from the backcross exhibited glyphosate tolerance. Furthermore, the expression of foreign proteins in the backcross offspring was notably lower than in the transgenic soybean, and there was no significant difference when compared to the hybrid progeny. Parameters such as germination rate, aboveground biomass, pods per plant, full seeds per plant, and 100-grain weight exhibited no significant differences between the negative and positive lines of the backcross progenies, and no fitness cost was identified in comparison to wild soybeans. These results underscore the potential for foreign genes to propagate within other wild soybeans, which requires continuous attention. Conclusions The widespread adoption of genetically modified soybeans has undeniably led to substantial economic gains. However, the research findings emphasize the critical importance of addressing the ecological risks posed by genetic drift towards wild soybeans. The backcross progeny system established in this study indicates that the potential for foreign gene dissemination to wild soybean populations warrants continued attention and mitigation strategies.

Abstract Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients’ samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

Abstract Background In China, parents who have lost their only child are referred to as Shidu parents (SDPs). This study aimed to investigate the prevalence and risk factors of post-traumatic stress disorder (PTSD) and investigate the influence of depressive and anxiety symptoms on the development of PTSD. Method Four hundred and thirty-six SDPs completed assessments of PTSD (Structured Clinical Interview for DSM-IV Disorders, SCID-IV; The Clinician-Administered PTSD Scale-IV, CAPS-IV), depression (Hamilton depression scale), and anxiety (Hamilton Anxiety Scale) via in-person interviews. Logistic regression and hierarchical multiple linear regression analyses were used to explore the association of demographic characteristics, depression, and anxiety symptoms with PTSD. Results The prevalence of PTSD in SDPs was 14.45%. The comorbidity of depression and anxiety symptoms was 87.30% in the SDPs with PTSD. The logistic regression model, which included factors of gender, age, education, depression, and anxiety, which contributed to the development of PTSD, was significant [χ² (11) = 122.47, p

Abstract Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.

Abstract Background With global climate change, the health threats of ambient high temperature have received widespread attention. However, latest spatio-temporal patterns of the non-communicable diseases (NCDs) burden attributable to high temperature have not been systematically reported. We aimed to analyze vulnerable areas and populations based on a detailed profile for the NCDs burden attributable to high temperature globally. Methods We obtained data from the Global Burden of Diseases (GBD) Study (2019) to describe the temporal and spatial patterns of NCDs burden attributable to high temperature globally from 1990–2019. Then we analyzed the differences by region, sex, and socio-demographic index (SDI). Finally, the age‑period‑cohort (APC) model was utilized to explore the age, period, and cohort effects of NCDs mortality caused by high temperature. Results In 2019, the number of deaths and Disability-adjusted life years (DALYs) from high-temperature-related NCDs was about 150,000 and 3.4 million globally, of which about 70% were in South Asia and North Africa and Middle East, and the burden was higher in men. Among 204 countries and territories, the highest age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were observed in Oman and United Arab Emirates, respectively. The global burden showed an upward trend from 1990 to 2019, with an EAPC of 3.66 (95%CI: 3.14–4.18) for ASMR and 3.68 (95%CI: 3.16-4.21) for ASDR. Cardiovascular diseases were the main contributors to the global burden of high-temperature-related NCDs in 2019. The age and period effect in APC model showed an increasing trend globally. There was a significant negative correlation between SDI and both ASMR (r = -0.17) and ASDR (r = -0.20) from 1990 to 2019. Conclusion There was an increasing trend of the global burden of high-temperature-related NCDs. The burden was likely to be higher in males and the elderly, as well as in countries and regions with less economically and socially developed and in tropical climates. Surveillance and prevention measures should be implemented with a focus on these vulnerable areas and susceptible populations.

Abstract Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline’s additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures. Graphical Abstract

Abstract Background Narrative nursing is a novel approach according with humanistic care, which has been shown to be effective in improving health outcomes for both patients and nurses. Nevertheless, few studies have investigated the status of narrative nursing practice among nurses, and a comprehensive understanding of factors influencing this practice remains elusive. Design This was an observational, cross-sectional study using convenience sampling method. Methods After obtaining the informed consent, a total of 931 registered nurses from three hospitals in China were investigated. Data were collected using the Social Support Rating Scale, the General Self-efficacy Scale, and the Knowledge-Attitude-Practice Survey of Clinical Nurses on Narrative Nursing. All the scales were validated in the Chinese population. The questionnaire results were verified by an independent investigator. Factors influencing narrative nursing practice were determined through a series of analyses, including independent sample t-tests, one-way ANOVA, and Pearson correlations. Subsequently, path analysis was performed and a structural equation model was established. Results The score of narrative nursing practice in this study was 30.26 ± 5.32. The structural equation model showed a good fit, with a Root Mean Square Error of Approximation (RMSEA) of 0.007 (90%CI: 0.000, 0.047). Both social support and narrative nursing attitude could directly affect narrative nursing practice (βsocial support = 0.08, P

Abstract Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What’s more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment. Graphical Abstract

Objective: To develop a deep learning model to predict lymph node (LN) status in clinical stage IA lung adenocarcinoma patients. Methods: This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets (699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital) between January 2005 and December 2019. The Cancer Hospital dataset was randomly split into a training cohort (559 patients) and a validation cohort (140 patients) to train and tune a deep learning model based on a deep residual network (ResNet). The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model. Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography (HRCT) features for the model. The predictive performance was assessed by area under the curves (AUCs), accuracy, precision, recall, and F1 score. Subgroup analysis was performed to evaluate the potential bias of the study population. Results: A total of 1,009 patients were included in this study; 409 (40.5%) were male and 600 (59.5%) were female. The median age was 57.0 years (inter-quartile range, IQR: 50.0–64.0). The deep learning model achieved AUCs of 0.906 (95% CI: 0.873–0.938) and 0.893 (95% CI: 0.857–0.930) for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule (non-pGGN) testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.622). The precisions of this model for predicting pN0 disease were 0.979 (95% CI: 0.963–0.995) and 0.983 (95% CI: 0.967–0.998) in the testing cohort and the non-pGGN testing cohort, respectively. The deep learning model achieved AUCs of 0.848 (95% CI: 0.798–0.898) and 0.831 (95% CI: 0.776–0.887) for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.657). The recalls of this model for predicting pN2 disease were 0.903 (95% CI: 0.870–0.936) and 0.931 (95% CI: 0.901–0.961) in the testing cohort and the non-pGGN testing cohort, respectively. Conclusions: The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

Tebufenozide, an efficient insect growth regulator (IGR) against lepidopteran pests, presents a novel mode of action with minimal non-target impact. By competing with ecdysteroids for ecdysone receptor (EcR) binding, it regulates insect growth precisely. This study explores tebufenozide's potential as a multitarget IGR, targeting both EcR and Ostrinia furnacalis chitinase I (OfChtI). The inhibitory activity against OfChtI is comparable to that of substrates (GlcNAc)5, with an IC50 of 45.77 ​μM. Our computational findings indicate that tebufenozide binds at the subsite −1 to +1 of OfChtI through various interactions. Notably, tebufenozide establishes a pi-pi interaction with the flipped sidechain of Trp107, enabling tebufenozide to deeply penetrate into the S1 pocket, thereby obstructing substrate binding to OfChtI. These insights highlight the potency of multitarget strategies, laying the groundwork for innovative IGR designs that offer comprehensive pest management solutions.

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Oral administration is the most simple, noninvasive, convenient treatment. With the increasing demands on the targeted drug delivery, the traditional oral treatment now is facing some challenges: 1) biologics how to implement the oral treatment and ensure the bioavailability is not lower than the subcutaneous injections; 2) How to achieve targeted therapy of some drugs in the gastrointestinal tract? Based on these two issues, drug delivery microrobots have shown great application prospect in oral drug delivery due to their characteristics of flexible locomotion or driven ability. Therefore, this paper summarizes various drug delivery microrobots developed in recent years and divides them into four categories according to different driving modes: magnetic-controlled drug delivery microrobots, anchored drug delivery microrobots, self-propelled drug delivery microrobots and biohybrid drug delivery microrobots. As oral drug delivery microrobots involve disciplines such as materials science, mechanical engineering, medicine, and control systems, this paper begins by introducing the gastrointestinal barriers that oral drug delivery must overcome. Subsequently, it provides an overview of typical materials involved in the design process of oral drug delivery microrobots. To enhance readers' understanding of the working principles and design process of oral drug delivery microrobots, we present a guideline for designing such microrobots. Furthermore, the current development status of various types of oral drug delivery microrobots is reviewed, summarizing their respective advantages and limitations. Finally, considering the significant concerns regarding safety and clinical translation, we discuss the challenges and prospections of clinical translation for various oral drug delivery microrobots presented in this paper, providing corresponding suggestions for addressing some existing challenges.

Background: The global prevalence of diabetic heart complication has been on the increase, and some of the drugs that are currently used to treat diabetes mellitus (DM) have not been able to mitigate this complication. Objective: This study determines the effect of Brazil nut (Bertholletia excelsa) and metformin on diabetic cardiomyopathy (DCM) in fructose/streptozotocin (STZ)-induced type 2 diabetic rats and also characterizes using Gas Chromatography Mass Spectrophotometry and Fourier Transform Infrared the bioactive compounds in 50% aqueous ethanol extract of Brazil nut. Design: After inducing type 2 DM, 30 male albino Wistar rats were separated into five groups that comprised of six rats per group, and they were treated as follows: groups 1 (Control) and 2 (Diabetic control) rats received rat pellets and distilled water; group 3 (Diabetic + Brazil nut) received rat pellets and Brazil nut extract (100 mg/kg, orally) dissolved in distilled water, group 4 (Diabetic + metformin) received metformin (100 mg/kg, orally) dissolved in distilled water, while group 5 (Diabetic + Brazil nut + metformin) received oral administrations of Brazil nut (100 mg/kg) and metformin (100 mg/kg) dissolved in distilled water. This study lasted for 6 weeks. The dose of Brazil nut used was selected from our pilot study on the minimum therapeutic dose of different concentrations of Brazil nut extract. Results: STZ administration induced insulin resistance, hyperglycemia, loss of weight, dyslipidemia, oxidative stress, inflammation, apoptosis, alteration of mammalian target of rapamycin, mitogen-activated protein kinase, heart function markers (creatine kinase MB, lactate dehydrogenase, and aspartate amino transaminase), and heart histology of the diabetic control, which was ameliorated after treatment with Brazil nut and metformin, but their combined treatment was better than the single treatments. Conclusion: This study shows that Brazil nut contains several bioactive compounds that support its biological properties as well as its candidature as a complementary therapy to metformin in mitigating cardiac complications arising from DM in rats.

Abstract The planthopper Nilaparvata muiri is a sister species to N. lugens (Hemiptera: Delphacidae), a notorious insect pest in Asian rice fields. N. muiri and N. lugens have a different host preference despite the similarities in many biological features. To better understand the adaptive evolution of planthoppers, comprehensive genomic information on N. muiri and N. lugens are urgently needed. In this study, we used ultra-low input PacBio HiFi libraries and Hi-C sequencing technologies to assemble a reference genome of a single N. muiri at the chromosomal level. The genome size was determined to be 531.62 Mb with a contig N50 size of 2.47 Mb and scaffold N50 size of 38.37 Mb. Totally, 96.61% assembled sequences were anchored to the 15 pseudo-chromosomes. BUSCO analysis yielded an Insecta completeness score of 98.6%. A total of 22,057 protein-coding genes were annotated, and 168.16 Mb repetitive sequences occupying 31.63% of genome were pinpointed. The assembled genome is valuable for evolutionary and genetic studies of planthoppers, and may provide sights to pest control.

Abstract Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.

Abstract Accurate prediction of the recovery of Disorders of Consciousness (DoC) is of paramount significance for clinicians and families. Serum total bilirubin (TBIL) formed by activation of heme oxygenase 2, is associated with incidence and prognosis of cardiovascular and cerebrovascular diseases. However, studies that based TBIL and DoC are limited. The study attempted to examine the association between serum TBIL levels and prognosis in patients with DoC. One hundred and sixty-eight patients with DoC in the Second hospital of Shandong University from June 2021 to June 2023 were recruited. The clinical characteristics and venous blood samples were collected within 24 h after admission. The diagnosis of DoC was determined by two skilled investigators employing various behavioral evaluations along the coma recovery scale-revised (CRS-R) and the investigators conducted follow-up assessments of diagnosis at 1, 3, and 6 months after admission. For statistical analysis, we categorized patients with an improvement in clinical diagnosis from study entry as having a “good outcome”. In total, 139 individuals enrolled in the study. The median TBIL level was 8.2 μmol/L. Good recovery of DoC at 1, 3, and 6 months occurred in 25 (18.0%), 41 (29.5%), and 56 (40.3%) patients, respectively. After full adjustment, a significant association was found between TBIL levels and the prognosis of DoC at 1, 3, and 6 months. When TBIL levels were analyzed as categorical variables, an increasing trend in the tertiles of TBIL levels demonstrated a significant positive association with the recovery of DoC at 1, 3, and 6 months. Stratified analysis revealed that the association between serum TBIL levels and the recovery of DoC remained consistent across different sub-populations. A high serum TBIL level is associated with an improved likelihood of recovery of DoC. Additional research is required to elucidate the underlying pathophysiological causal association between TBIL levels and DoC.

Abstract Background Nearly three in four U.S. medical students graduate with debt in six-figure dollar amounts which impairs students emotionally and academically and impacts their career choices and lives long after graduation. Schools have yet to develop systems-level solutions to address the impact of debt on students’ well-being. The objectives of this study were to identify students at highest risk for debt-related stress, define the impact on medical students’ well-being, and to identify opportunities for intervention. Methods This was a mixed methods, cross-sectional study that used quantitative survey analysis and human-centered design (HCD). We performed a secondary analysis on a national multi-institutional survey on medical student wellbeing, including univariate and multivariate logistic regression, a comparison of logistic regression models with interaction terms, and analysis of free text responses. We also conducted semi-structured interviews with a sample of medical student respondents and non-student stakeholders to develop insights and design opportunities. Results Independent risk factors for high debt-related stress included pre-clinical year (OR 1.75), underrepresented minority (OR 1.40), debt $20–100 K (OR 4.85), debt >$100K (OR 13.22), private school (OR 1.45), West Coast region (OR 1.57), and consideration of a leave of absence for wellbeing (OR 1.48). Mental health resource utilization (p = 0.968) and counselors (p = 0.640) were not protective factors against debt-related stress. HCD analysis produced 6 key insights providing additional context to the quantitative findings, and associated opportunities for intervention. Conclusions We used an innovative combination of quantitative survey analysis and in-depth HCD exploration to develop a multi-dimensional understanding of debt-related stress among medical students. This approach allowed us to identify significant risk factors impacting medical students experiencing debt-related stress, while providing context through stakeholder voices to identify opportunities for system-level solutions.

Abstract Objective To investigate pantothenate kinases 1 (PANK1) expression in kidney renal clear cell carcinoma (KIRC) tissues, analyze its correlation with clinicopathological features and prognosis, and explore its impact on invasion, migration, and apoptosis in KIRC cells. Methods GEPIA (gene expression profiling interactive analysis), UALCAN and LinkedOmics, were employed to analyze PANK1 expression in KIRC tissues and its correlation with clinical characteristics. Comparative analyses were performed between KIRC (Caki-1 and 786-O) and noncancerous renal cells (HK-2 and RPTEC). Transfection with PANK1 activation particles was conducted, followed by Wound healing, Transwell assay, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and Western blotting. Results PANK1 was down-regulated in KIRC tissues and cells compared to normal tissues and noncancerous cells. Correlation analyses linked PANK1 expression with clinicopathological features in KIRC, with high PANK1 expression associated with a favorable outcome. High PANK1 expression correlated positively with E-cadherin (CDH1), tight junction protein 1 (TJP1), Fas cell surface death receptor (FAS), caspase-8 (CASP8), and CASP9, while showing a negative correlation with vimentin (VIM), snail family transcriptional repressor 1 (SNAIL1), twist family BHLH transcription factor 1 (TWIST1), and TWIST2. PANK1 overexpression increased CDH1, TJP1, FAS, CASP8, and CASP9 while downregulating SNAIL1, VIM, TWIST1, and TWIST2, inhibiting invasion and migration, and promoting apoptosis in KIRC cells. Conclusion PANK1 down-regulation in KIRC tissues correlated with clinicopathological features and prognosis. Its overexpression modulated epithelial-mesenchymal transition (EMT)-related gene, inhibited invasion, promoted apoptosis in KIRC cells, highlighting its role in disease progression and therapeutic potential.

Abstract Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes.

Abstract The long-term interaction between the environment and humans has significantly shaped contemporary landscapes worldwide. As a heritage landscape, the polder is essential for understanding the impact of the past human activities on contemporary landscape on low-lying area of land. In this case study, we reconstructed the regional spatial distribution of the polders in the early twentieth century and examined their coherence over the past century using historical maps and other materials in the Jianghan Plain. The results revealed several key findings: (1) In the early twentieth century, there were 1571 polders covering an area of 11,826.1 km2 with a perimeter of 17,035.9 km. (2) These polders exhibited a J-shaped distribution, with few large-scale polders despite their substantial areas. (3) The shape of these polders reflected an ability to balance human needs and the natural environment. (4) Considerable regional differences in these polders were attributed to centuries-old interactions between humans and the environment. (5) The remnants of these early twentieth century polders have had a lasting influence on the contemporary landscape, particularly in rural areas. This case study underscores how taking into account a broader historical perspective can enhance our understanding of present-day landscapes and, more importantly, the role that past human actions have played in shaping them.

Abstract Background Gallbladder cancer (GBC) is characterized by high mortality rate. Our study sought therapeutic candidates for GBC. Results Bioinformatics analysis identified significant upregulation of MST1R in GBC. In vitro experiments demonstrated that the MST1R inhibitor MGCD-265 effectively restrained GBC cell proliferation at lower concentrations. Additionally, it induced cycle arrest and apoptosis in GBC cells in a dose-dependent manner. Mouse models exhibited that MGCD-265 treatment significantly diminished the proliferative capacity of GBC-SD cells. Transcriptomics sequencing revealed significant transcriptome alterations, with 200 transcripts upregulated and 883 downregulated. KEGG and GO analyses highlighted enrichment in processes like cell adhesion and pathways such as protein digestion and absorption. Downstream genes analysis identified JMJD6 upregulation post-MGCD-265 treatment. In vivo experiments confirmed that combining MGCD-265 with the JMJD6 inhibitor SKLB325 enhanced the anticancer effect against GBC. Conclusion Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.

Abstract The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P

Abstract Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.

Abstract Purpose The atherogenic index of plasma (AIP) is a novel comprehensive lipid index. We aimed to investigate a possible relationship between AIP index and kidney stones in US adults. Methods This cross-sectional study was conducted among adults with complete AIP index and questionnaire records on kidney stones from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. The AIP index served as the exposure variable, defined as the logarithm of the ratio between triglycerides (TG, mmol/L) and high-density lipoprotein cholesterol (HDL-c, mmol/L). Self-reported history of kidney stones was utilized as the outcome variable. The independent relationship between AIP index and the risk of kidney stones was fully assessed. Results A total of 14,833 participants were included in this study, with an average AIP index of -0.07 ± 0.01. The proportion of kidney stones progressively increased with higher AIP index tertile intervals (7.33% vs. 9.97% vs. 12.57%, P 0.05). Conclusions The AIP index may be a potential epidemiological tool to quantify the role of dyslipidemia in the risk of kidney stones in US adults.

A new bamboo species, Yushania dezhui, from Kunming, Yunnan, China is described and illustrated in this paper. The new species used to be misidentified as Y. polytricha. Based on careful comparison of morphological features and molecular phylogeny evidence, we confirmed its identity as a new member of the genus Yushania. Yushania dezhui resembles Y. maculata, Y. polytricha and Y. weixiensis in several aspects, such as culm height and branch complement structure. However, the glabrous culm leaf sheaths and internodes, the absence of auricles and oral setae on most foliage leaves, except the one-year-old foliage leaves, the pubescence on the adaxial surface of the one-year-old foliage leaves and its limestone habitat preference can readily distinguish this new species from its related taxa. Moreover, we emphasise that individuals from various populations and molecular markers with different inheritance patterns for phylogeny reconstruction should be included in new species discovery, especially in plant groups with complex evolutionary histories.

Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and lethal tumor with poor prognosis. Its survival period ranges from four months to one year, and the 5-year survival rate is only about 10%. MPM is highly resistant to chemotherapy, and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20% of patients. In recent years, with the continuous in-depth understanding of the genetic variation characteristics of MPM, some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM. This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM, including BAP1 gene mutation, microRNA, MTA1-mediated DNA damage repair pathway, GITR-GITRL pathway, TGFa pathway, tumor stem cell, EGFR, and PTEN. The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM.

Abstract Research on the severity and prognosis of sepsis with or without progressive delirium is relatively insufficient. We constructed a prediction model of the risk factors for 28-day mortality in patients who developed sepsis or sepsis-associated delirium. The modeling group of patients diagnosed with Sepsis-3 and patients with progressive delirium of related indicators were selected from the MIMIC-IV database. Relevant independent risk factors were determined and integrated into the prediction model. Receiver operating characteristic (ROC) curves and the Hosmer–Lemeshow (HL) test were used to evaluate the prediction accuracy and goodness-of-fit of the model. Relevant indicators of patients with sepsis or progressive delirium admitted to the intensive care unit (ICU) of a 3A hospital in Xinjiang were collected and included in the verification group for comparative analysis and clinical validation of the prediction model. The total length of stay in the ICU, hemoglobin levels, albumin levels, activated partial thrombin time, and total bilirubin level were the five independent risk factors in constructing a prediction model. The area under the ROC curve of the predictive model (0.904) and the HL test result (χ2 = 8.518) indicate a good fit. This model is valuable for clinical diagnosis and treatment and auxiliary clinical decision-making.

Abstract Background Chinese Cymbidium orchids, cherished for their deep-rooted cultural significance and significant economic value in China, have spawned a rich tapestry of cultivars. However, these orchid cultivars are facing challenges from insufficient cultivation practices and antiquated techniques, including cultivar misclassification, complex identification, and the proliferation of counterfeit products. Current commercial techniques and academic research primarily emphasize species identification of orchids, rather than delving into that of orchid cultivars within species. Results To bridge this gap, the authors dedicated over a year to collecting a cultivar image dataset for Chinese Cymbidium orchids named Orchid2024. This dataset contains over 150,000 images spanning 1,275 different categories, involving visits to 20 cities across 12 provincial administrative regions in China to gather pertinent data. Subsequently, we introduced various visual parameter-efficient fine-tuning (PEFT) methods to expedite model development, achieving the highest top-1 accuracy of 86.14% and top-5 accuracy of 95.44%. Conclusion Experimental results demonstrate the complexity of the dataset while highlighting the considerable promise of PEFT methods within flower image classification. We believe that our work not only provides a practical tool for orchid researchers, growers and market participants, but also provides a unique and valuable resource for further exploring fine-grained image classification tasks. The dataset and code are available at https://github.com/pengyingshu/Orchid2024 .

Abstract Mechanochemistry studies the effect of mechanical force on chemical bonds, bringing opportunities for synthesizing alloys, ceramics, organics, polymers, and biomaterials. A vital issue of applying macro-scale mechanical force to manipulate crystal structures is finding ways to precisely adjust the force directions to break micro-scale target chemical bonds. Inspired by a common technique of driving a wedge into the wood to make wood chopping much easier, a wedging strategy of splitting three-dimensional structured crystalline frameworks and then converting them to nanosheets was proposed, where specific molecules were wedged into crystalline frameworks to drive the directional transmission of mechanical force to break chemical bonds. As a result, various crystalline framework nanosheets including metal−organic framework nanosheets, covalent organic framework nanosheets, and coordination polymer nanosheets were fabricated. This wedging crystal strategy exhibits advantages of operability, flexibility and designability, and furthermore, it is expected to expand mechanochemistry applications in material preparation.

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Abstract Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Abstract Proteasome inhibitors (PIs), such as bortezomib and calfizomib, were backbone agents in the treatment of multiple myeloma (MM). In this study, we investigated bortezomib interactors in MM cells and identified dihydrolipoamide dehydrogenase (DLD) as a molecular target of bortezomib. DLD catalyzes the oxidation of dihydrolipoamide to form lipoamide, a reaction that also generates NADH. Our data showed that bortezomib bound to DLD and inhibited DLD’s enzymatic function in MM cells. DLD knocked down MM cells (DLD-KD) had decreased levels of NADH. Reduced NADH suppressed assembly of proteasome complex in cells. As a result, DLD-KD MM cells had decreased basal-level proteasome activity and were more sensitive to bortezomib. Since PIs were used in many anti-MM regimens in clinics, we found that high expression of DLD correlated with inferior prognosis of MM. Considering the regulatory role of DLD in proteasome assembly, we evaluated DLD targeting therapy in MM cells. DLD inhibitor CPI-613 showed a synergistic anti-MM effect with bortezomib in vitro and in vivo. Overall, our findings elucidated DLD as an alternative molecular target of bortezomib in MM. DLD-targeting might increase MM sensitivity to PIs.

Abstract Background Ischemia reperfusion (IR) causes impaired myocardial function, and autophagy activation ameliorates myocardial IR injury. Isoliquiritigenin (ISO) has been found to protect myocardial tissues via AMPK, with exerting anti-tumor property through autophagy activation. This study aims to investigate ISO capacity to attenuate myocardial IR through autophagy activation mediated by AMPK/mTOR/ULK1 signaling. Methods ISO effects were explored by SD rats and H9c2 cells. IR rats and IR-induced H9c2 cell models were established by ligating left anterior descending (LAD) coronary artery and hypoxia/re-oxygenation, respectively, followed by low, medium and high dosages of ISO intervention (Rats: 10, 20, and 40 mg/kg; H9c2 cells: 1, 10, and 100 μmol/L). Myocardial tissue injury in rats was assessed by myocardial function-related index, HE staining, Masson trichrome staining, TTC staining, and ELISA. Autophagy of H9c2 cells was detected by transmission electron microscopy (TEM) and immunofluorescence. Autophagy-related and AMPK/mTOR/ULK1 pathway-related protein expressions were detected with western blot. Results ISO treatment caused myocardial function improvement, and inhibition of myocardial inflammatory infiltration, fibrosis, infarct area, oxidative stress, CK-MB, cTnI, and cTnT expression in IR rats. In IR-modeled H9c2 cells, ISO treatment lowered apoptosis rate and activated autophagy and LC3 fluorescence expression. In vivo and in vitro, ISO intervention exhibited enhanced Beclin1, LC3II/LC3I, and p-AMPK/AMPK levels, whereas inhibited P62, p-mTOR/mTOR and p-ULK1(S757)/ULK1 protein expression, activating autophagy and protecting myocardial tissues from IR injury. Conclusion ISO treatment may induce autophagy by regulating AMPK/mTOR/ULK1 signaling, thereby improving myocardial IR injury, as a potential candidate for treatment of myocardial IR injury.

Abstract Background The efficacy of highly restrictive dietary therapies such as exclusive enteral nutrition (EEN) in the induction of remission in Crohn’s disease (CD) are well established, however, ongoing issues exist with its poor palatability, restrictions, and adherence. The primary aim of this review is to evaluate the current evidence for the efficacy of exclusively solid food diets on the induction and maintenance of clinical and biochemical remission in CD. Secondary aims include impact on endoscopic healing and quality of life. Methods A systematic review of all randomised controlled trials (RCTs), open-label randomised trials and head-to-head clinical trials assessing solid food diet intervention in patients with active or inactive Crohn’s disease was conducted. Studies included adult and paediatric patients with a verified disease activity index at baseline and follow up (Harvey Bradshaw Index, HBI; Crohn’s disease activity index, CDAI and paediatric CDAI, PCDAI). Additional secondary endpoints varied between studies, including endoscopic and biochemical responses, as well as quality of life measures. Two authors independently performed critical appraisals of the studies, including study selection and risk of bias assessments. Results 14 studies were included for review, with several studies suggesting clinically significant findings. Clinical remission was achieved in a paediatric population undertaking the Mediterranean diet (MD) (moderate risk of bias). In adults, the Crohn’s disease exclusion diet (CDED) was comparable to the CDED with partial enteral nutrition (PEN) diet in induction of remission (moderate risk of bias). A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet was also shown to decrease symptoms in patients with quiescent or mildly active CD (high risk of bias), however, this was not corroborated by other low FODMAP diet studies. Conclusions There are promising outcomes for the MD and CDED in inducing clinical remission in mild to moderate CD. The results need to be interpreted with caution due to design limitations, including issues with combining outcomes among CD and UC patients, and small sample size. The current evidence for solid food dietary therapy in CD is limited by the lack of high quality studies and moderate to high bias. Future well designed studies are needed to confirm their efficacy.

Abstract Polymer nanocomposites with tuning functions are exciting candidates for various applications, and most current research has focused on static mechanical reinforcement. Actually, under service conditions of complex dynamic interference, stable dynamic mechanical properties with high energy dissipation become more critical. However, nanocomposites often exhibit a trade-off between static and dynamic mechanics, because of their contradictory underlying physics between chain crosslinking and chain relaxation. Here, we report a general strategy for constructing ultra-stable dynamic mechanical complex fluid nanocomposites with high energy dissipation by infusing complex fluids into the nanoconfined space. The key is to tailor full-scale polymer dynamics across an exceptionally broad timescale by single-chain confinement. These materials exhibit stable storage modulus (100 ~ 102 MPa) with high energy dissipation (loss factor > 0.4) over a broad frequency range (10−1 ~ 107 Hz)/temperature range (−35 ~ 85°C). In the loss factor > 0.4 region, their dynamic mechanical stability (rate of modulus change versus temperature (k)) is 10 times higher than that of conventional polymer nanocomposites.

Abstract Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1–5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.

Abstract Background To explore whether nobiletin has a protective effect on high-fat diet (HFD)-induced enteric nerve injury and its underlying mechanism. Methods An obesity model was induced by a HFD. Nobiletin (100 mg/kg and 200 mg/kg) and vehicle were administered by gastric gavage for 4 weeks. Lee’s index, body weight, OGTT and intestinal propulsion assays were performed before sacrifice. After sampling, lipids were detected using Bodipy 493/503; lipid peroxidation was detected using MDA and SOD kits and the expression of PGP 9.5, Trem2, GFAP, β-tubulin 3, Bax, Bcl2, Nestin, P75 NTR, SOX10 and EDU was detected using immunofluorescence. The GDNF, p-AKT, AKT, p-FOXO3a, FOXO3a and P21 proteins were detected using western blotting. The relative mRNA expression levels of NOS2 were detected via qPCR. Primary enteric neural stem cells (ENSCs) were cultured. After ENSCs were treated with palmitic acid (PA) and nobiletin, CCK-8 and caspase-3/7 activity assays were performed to evaluate proliferation and apoptosis. Results HFD consumption caused colon lipid accumulation and peroxidation, induced enteric nerve damage and caused intestinal motor dysfunction. However, nobiletin reduced lipid accumulation and peroxidation in the colon; promoted Trem2, β-tubulin 3, Nestin, P75NTR, SOX10 and Bcl2 expression; inhibited Bax and GFAP expression; reduced NOS2 mRNA transcription; and regulated the GDNF/AKT/FOXO3a/P21 pathway. Nobiletin also promoted PA-induced impairment of ENSCs. Conclusions Nobiletin restored HFD-induced enteric nerve injury, which may be associated with inhibiting enteric nerve apoptosis, promoting enteric nerve survival and regulating the GDNF/AKT/FOXO3a/P21 pathway.