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C(sp 3 ) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp 3 )-C(sp 3 ) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives., (© 2024 Wiley-VCH GmbH.)

Gemcitabine-based monotherapy or combination therapy has become the standard treatment for locally advanced and metastatic pancreatic cancer. However, the emergence of resistance within weeks of treatment severely compromises therapeutic efficacy. The intricate biological process of gemcitabine resistance in pancreatic cancer presents a complex challenge, as the underlying mechanisms remain unclear. Identifying the target protein of gemcitabine is crucial for studying its drug-resistance mechanism. An activity-based probe is a powerful tool for studying drug target proteins, but the current lack of activity-based gemcitabine probes with robust biological activity hinders research on gemcitabine. In this study, we developed three active probes based on gemcitabine, among which Gem-3 demonstrated excellent stability and labeling efficacy. We utilized Gem-3 in conjunction with chemical proteomics to identify intracellular target proteins. We identified 79 proteins that interact with gemcitabine, most of which were previously unknown and represented various functional classes. Additionally, we validated the increased expression of IFIT3 and MARCKS in drug-resistant cells, along with the activation of the NF-κB signaling pathway. These findings substantially contribute to our comprehension of gemcitabine's target proteins and further our understanding of the mechanisms driving gemcitabine resistance in pancreatic cancer cells.

Compared to the surface defect detection of industrial products produced according to specified processes, the detection of surface defects in naturally grown red jujubes poses unique and significant challenges for researchers. The high diversity of surface defects, subtle distinctions from the background, low contrast, varying scales, and the presence of high levels of noise in images are among the factors that greatly amplify the complexity of defect detection tasks. Existing methods show some deficiencies in addressing these issues, mainly due to insufficient feature extraction capabilities and overly complex network structures, leading to limitations in model efficiency and practical application performance. To tackle the challenges associated with red jujube surface defect detection, this study proposes an optimized Tiny Vision Transformer (TinyViT) network structure, named RJ-TinyViT. This method refines the TinyViT-5 m network structure to reduce network burden and introduces an improved Multi-Kernel Block (MK Block) and an improved Mobile Inverted Bottleneck Convolution Block (MBConv Block) to enhance feature extraction capabilities. Additionally, we have integrated the Coordinate Attention (CA) module to enhance the model's capacity for recognizing and focusing on features of surface defects on red jujubes. Experimental results show that RJ-TinyViT achieved a classification accuracy of 93.38%, marking an improvement of 1.84% over the original TinyViT network. At the same time, its Floating-point Operations (FLOPs) and Parameters (Params) were reduced to 58.97% and 39.84% of the original TinyViT network, respectively. These results not only demonstrate that RJ-TinyViT achieves model lightweighting while maintaining high accuracy but also highlight its value in practical industrial applications., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Hydrogels with abundant water and responsiveness to external stimuli have emerged as promising candidates for artificial muscles and garnered significant interest for applications as soft actuators and robots. However, most hydrogels possess amorphous structures and exhibit slow, isotropic responses to external stimuli. These features are far inferior to real muscles, which have ordered structures and endow living organisms with programmable deformations and motions through fast, anisotropic responses in complex environments. In recent years, this issue has been addressed by a conceptual new strategy to develop muscle-like hydrogels with highly oriented nanosheets. These hydrogels exhibit fast, isochoric responses based on temperature-mediated electrostatic repulsion between charged nanosheets rather than water diffusion, which significantly advances the development of soft actuators and robots. This minireview summarizes the recent progress in muscle-like hydrogels and their applications as soft actuators and robots. We first introduce the synthesis of muscle-like hydrogels with monodomain structures and the unique mechanism for rapid and isochoric deformations. Then, the developments of hydrogels with complex ordered structures and hydrogel-based soft robots are discussed. The morphing mechanisms and motion kinematics of the hydrogel actuators and robots are highlighted. Finally, concluding remarks are given to discuss future opportunities and challenges in this field.

Background: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disorder for which there is currently no cure, nor effective treatment strategy., Objective: Our aim was to investigate the safety and efficacy of high-dose ganglioside GM1 (ganglioside-monosialic acid) pulse treatment in patients with SCA3., Methods: Patients were randomly allocated to receive either high-dose GM1 (400 mg on the first day followed by 200 mg/day), low-dose GM1 (40 mg/day), or placebo (normal saline) for 4 weeks. The primary outcome, assessed by measuring the change in the Scale for the Assessment and Rating of Ataxia (SARA) scores from baseline to 12 weeks post-treatment, is central to evaluating treatment efficacy. Secondary outcomes included changes in the International Cooperative Ataxia Rating Scale (ICARS) score, Barthel Index of Activities of Daily Living (ADL), and plasma and cerebrospinal fluid (CSF) GABA levels. Safety was assessed in all treated patients., Results: A total of 48 patients with SCA3 were enrolled in this study. After 12 weeks, data from 43 patients were included in the efficacy analysis (intention-to-treat analysis). The least-squares mean change in the SARA score from baseline to 12 weeks post-treatment was -3.80 (standard error [SE], 0.39; 95% confidence interval [CI], -4.58 to -3.02) in the high-dose GM1 group, 0.34 (SE, 0.40; 95% CI, -0.46 to 1.13) in the low-dose GM1 group, and 0.73 (SE, 0.40; 95% CI, -0.07 to 1.52) in the placebo group, respectively. Secondary outcomes showed improvements in the ICARS score, Barthel Index of ADL, and plasma and CSF GABA levels in the high-dose GM1 group compared to the low-dose GM1 and placebo groups. All treatments were well-tolerated and safe., Conclusions: High-dose GM1 treatment significantly ameliorated ataxic symptoms in patients with SCA3. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3 + /CD8 + T lymphocytes and IL-4 + cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection., (© 2024. The Author(s).)

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) may be indicative of breast cancer (BC); however, this remains inconclusive. With the aim to assess the current literature to evaluate the diagnostic roles of NLR PLR and LMR in BC, a systematic literature search was performed using the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP database and China Biology Medicine disc databases up to August 29, 2023. The standardized mean deviation and 95% confidence intervals (CI) for each outcome was reported, and heterogeneity and publication bias were assessed. Overall, 39 studies were included in the present study. Pooled analysis with the random-effects model demonstrated that patients with BC had significantly higher NLR and PLR, and a lower LMR, compared with non-BC subjects. The pooled sensitivities of the NLR and PLR were 0.68 (95% CI, 0.59-0.75) and 0.55 (95% CI, 0.36-0.72), respectively, and the pooled specificities of the NLR and PLR were 0.75 (95% CI, 0.68-0.81) and 0.80 (95% CI, 0.51-0.94), respectively. However, the limited number of studies included hindered the evaluation of the diagnostic role of LMR. In summary, a higher NLR and PLR and lower LMR were associated with the presence of BC. NLR and PLR may be potential blood-based biomarkers for the differentiation of BC. Despite these findings, further studies are needed to validate their clinical applicability and practicality. International Prospective Register of Systematic Reviews registration no. CRD42024522226., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Yang et al.)

Photosynthesis is the largest flux of carbon between the atmosphere and Earth's surface and is driven by enzymes that require nitrogen, namely, ribulose-1,5-bisphosphate (RuBisCO). Thus, photosynthesis is a key link between the terrestrial carbon and nitrogen cycle, and the representation of this link is critical for coupled carbon-nitrogen land surface models. Models and observations suggest that soil nitrogen availability can limit plant productivity increases under elevated CO 2 . Plants acclimate to elevated CO 2 by downregulating RuBisCO and thus nitrogen in leaves, but this acclimation response is not currently included in land surface models. Acclimation of photosynthesis to CO 2 can be simulated by the photosynthetic optimality theory in a way that matches observations. Here, we incorporated this theory into the land surface component of the Energy Exascale Earth System Model (ELM). We simulated land surface carbon and nitrogen processes under future elevated CO 2 conditions to 2100 using the RCP8.5 high emission scenario. Our simulations showed that when photosynthetic acclimation is considered, photosynthesis increases under future conditions, but maximum RuBisCO carboxylation and thus photosynthetic nitrogen demand decline. We analyzed two simulations that differed as to whether the saved nitrogen could be used in other parts of the plant. The allocation of saved leaf nitrogen to other parts of the plant led to (1) a direct alleviation of plant nitrogen limitation through reduced leaf nitrogen requirements and (2) an indirect reduction in plant nitrogen limitation through an enhancement of root growth that led to increased plant nitrogen uptake. As a result, reallocation of saved leaf nitrogen increased ecosystem carbon stocks by 50.3% in 2100 as compared to a simulation without reallocation of saved leaf nitrogen. These results suggest that land surface models may overestimate future ecosystem nitrogen limitation if they do not incorporate leaf nitrogen savings resulting from photosynthetic acclimation to elevated CO 2 ., (© 2024 John Wiley & Sons Ltd.)

Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the progression of CKD, but the mechanisms behind it are not fully understood, making treatment options limited. Here, we find that the E3 ligase TRIM65 is a positive regulator of renal fibrosis. Deletion of TRIM65 results in a reduction of pathological lesions and renal fibrosis in mouse models of kidney fibrosis induced by unilateral ureteral obstruction (UUO)- and folic acid. Through screening with a yeast-hybrid system, we identify a new interactor of TRIM65, the mammalian cleavage factor I subunit CFIm25 (NUDT21), which plays a crucial role in fibrosis through alternative polyadenylation (APA). TRIM65 interacts with NUDT21 to induce K48-linked polyubiquitination of lysine 56 and proteasomal degradation, leading to the inhibition of TGF-β1-mediated SMAD and ERK1/2 signaling pathways. The degradation of NUDT21 subsequently altered the length and sequence content of the 3'UTR (3'UTR-APA) of several pro-fibrotic genes including Col1a1, Fn-1, Tgfbr1, Wnt5a, and Fzd2. Furthermore, reducing NUDT21 expression via hydrodynamic renal pelvis injection of adeno-associated virus 9 (AAV9) exacerbated UUO-induced renal fibrosis in the normal mouse kidneys and blocked the protective effect of TRIM65 deletion. These findings suggest that TRIM65 promotes renal fibrosis by regulating NUDT21-mediated APA and highlight TRIM65 as a potential target for reducing renal fibrosis in CKD patients., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Neuropathic pain is a significant and persistent issue for individuals with spinal cord injuries (SCI), severely impacting their quality of life. While changes at the peripheral and spinal levels are known to contribute to SCI-related pain, whether and how supraspinal centers contribute to post SCI chronic neuropathic pain is poorly understood. Here, we first validated delayed development of chronic neuropathic pain in mice with moderate contusion SCI. To identify supraspinal regions involved in the pathology of neuropathic pain after SCI, we next performed an activity dependent genetic screening and identified multiple cortical and subcortical regions that were activated by innocuous tactile stimuli at a late stage following contusion SCI. Notably, chemogenetic inactivation of pain trapped neurons in the lateral thalamus alleviated neuropathic pain and reduced tactile stimuli evoked cortical overactivation. Retrograde tracing showed that contusion SCI led to enhanced corticothalamic axonal sprouting and over-activation of corticospinal neurons. Mechanistically, ablation or silencing of corticospinal neurons prevented the establishment or maintenance of chronic neuropathic pain following contusion SCI. These results highlighted a corticospinal-lateral thalamic feed-forward loop whose activation is required for the development and maintenance of chronic neuropathic pain after SCI. Our data thus shed lights into the central mechanisms underlying chronic neuropathic pain associated with SCI and the development of novel therapeutic avenues to treat refractory pain caused by traumatic brain or spinal cord injuries., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

2-D carbon-based materials are well-known for their broadband absorption properties for efficient solar energy conversion. However, their high reflectivity poses a challenge for achieving efficient omnidirectional light absorption. Inspired by the multilevel structures of the flower, a Graphene Microflower (GM) material with gradient refractive index surface was fabricated on polymer substrates using the UV-intense laser-induced phase explosion technique under the synergistic design of the photothermal Marangoni effect and the fluid instability principle. The refractive index gradient reduces light reflection and absorbs at least 96% of light at incident angles of 0-60° across the entire solar wavelength range (200-2500 nm). Over 90% absorption even at 75° angle of incidence. The light absorption is enhanced by the multiple interferometric phase cancelation and localized surface plasmon resonance, resulting in a steady-state temperature 60 °C higher than ambient conditions under one solar irradiation. The max rate of temperature rise can reach up to 62 °C s -1 . The device is then integrated at the hot end of the temperature difference generator at high altitude to ensure continuous and efficient power generation, producing a steady-state power of 196 mW.

Janus transition metal dichalcogenides (TMDs) are a novel class of 2D materials with unique mirror asymmetry. Plasma-assisted synthesis at room temperature is favored for producing Janus TMDs due to its energy efficiency and prevention of alloying. However, current methods require stringent control over growth conditions, risking defects or unintended materials. A robust plasma-assisted (RPA) synthesis strategy is introduced, incorporating a built-in tube with a suitable inner diameter into the plasma-assisted system. This innovation creates a mild, uniform plasma atmosphere, allowing for broader variations in growth parameters without significantly affecting Janus MoSSe's morphology and characteristics. This approach simplifies the synthesis process and enhances the success rate of Janus TMD production. Additionally, methods are explored to enhance the photoluminescence (PL) of Janus MoSSe. Releasing MoSSe from the growth substrate and annealing it removes strain and unintentional doping, improving PL performance. MoSSe on hexagonal boron nitride (h-BN) flakes after annealing shows a 32-fold increase in PL intensity. Bis(trifluoromethane) sulfonimide (TFSI) treatment of MoSSe results in a remarkable 70-fold increase in PL intensity, a 2.5-fold extension in exciton lifetime, and quantum yield (QY) reaching up to ≈31.2%. These findings provide critical insights for optimizing the luminescence properties of 2D Janus materials, advancing Janus optoelectronics., (© 2024 Wiley‐VCH GmbH.)

The objective of this study was to ascertain the relationship between the weight-adjusted waist index (WWI) and the risk of stroke in an elderly hypertensive population, a relationship that has not been previously elucidated. The Cox regression model was employed to assess the correlation between baseline WWI measurements and the incidence of stroke. To further elucidate the shape of the association between baseline WWI and stroke, restricted cubic splines were employed. Furthermore, subgroup analyses and interaction tests were carried out to investigate potential heterogeneities. Our study cohort comprised 4962 hypertensive individuals aged 60 years or older with no prior history of stroke. Over a median follow-up of 3.2 years, we found 547 new-onset stroke cases. After adjusting for confounding variables, the Cox regression analysis revealed a positive association between baseline WWI and the risk of stroke, with hazard ratios (HRs) escalating progressively as WWI values increased. When compared to the lowest quartile of WWI, the highest quartile demonstrated an HR of 1.87 (95% CI, 1.44-2.42) for stroke. Subgroup analyses confirmed the consistency of this relationship across different demographic and clinical strata. The study findings indicate that an elevated WWI is significantly related with a higher risk of new-onset stroke among elderly patients with hypertension. These results underscore the importance of WWI as a potential risk stratification tool. To confirm these results and explore the causal mechanisms behind the observed correlation, more study is necessary., (© 2024. The Author(s).)

Piezocatalysis is considered to be a favorable catalytic technology by utilizing external mechanical stimulation to promote the specific redox reactions. The application of piezocatalysis in batteries is promising but faces formidable challenges. Herein, the operation principles of piezocatalysis were successfully demonstrated by constructing solid-state Li-Se and Li-S battery models with interfacial stress accumulation. Lead zirconate titanate with an ultra-high piezoelectric coefficient was applied as the piezoelectric catalyst. The uniformity of the dipole orientation in materials was essential for achieving piezocatalysis in batteries. The accumulated high-stress converts to piezopotential for catalyzing most reaction processes in batteries, while the rapid stress change prevents the internal charge reorganization, ensuring continuous efficient catalysis. The internal stress change alters the internal polarisation strength, driving excess screening charge to participate in the electrochemical reaction. Under piezocatalysis, solid-state Li-Se batteries exhibited a initial discharge capacity of 670.9 mAh g -1 (99.4 % of the theoretical value) at 0.1 C, and Li-S batteries showed a capacity of 1463 mAh g -1 at 0.2 C, which was still maintained up to 1084 mAh g -1 at an elevated rate of 0.5 C. This piezocatalysis strategy provides a strong theoretical basis and design specification for enhancing Li-Se and Li-S battery reaction kinetics., (© 2024 Wiley-VCH GmbH.)

The widespread prevalence of bovine coronavirus (BCoV) disease worldwide has impacted the livestock industry economically. No effective vaccine is available in China. In this study, we produced BCoV virus-like particles (VLPs) containing E, M, N, S, and hemagglutinin-esterase (HE) proteins using a baculovirus expression system. Five recombinant baculoviruses were co-infected with Sf9 cells, and the VLPs were assembled and characterized. Mice and cattle were immunized by VLPs mixed with MF59 and CpG 55.2 adjuvants. Two doses of the VLPs/MF59/CpG vaccine were administered in mice and cattle. The immune effect of the VLPs/MF59/CpG vaccine was measured using indirect ELISA and neutralization assays. After immunization, the serum IgG-specific antibody titer against S protein and neutralization antibody titer increased to 1:1.28 × 10 4 (p < 0.01) and 1:128 (p < 0.01) in mice, respectively. Interestingly, the high IgG antibody and neutralizing antibody titers were maintained for seven days in mice. In addition, the serum IgG-specific antibody titer against S proteins and neutralization antibody titer increased to 1:1.024 × 10 5 and 1:512 (p < 0.05) in cattle, respectively. The high IgG antibody and neutralizing antibody titers were maintained for 21 days in cattle. Notably, BCoV VLPs group interferon-gamma (IFN-γ) lymphocytes in spleens were significantly increased (p < 0.01). These findings suggest that BCoV VLPs induced strong cellular and humoral immune responses in mice and cattle. These findings suggest that BCoV VLPs could serve as a potent immunogen for vaccine development., Competing Interests: Declaration of competing interest The authors declared no conflicts of interest regarding the research, authorship, and publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT., Method: We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked., Results: A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p < 0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5 Mb in size, and nine (13.85%) were between 5 and 10 Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p < 0.05)., Conclusions: Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis., (© 2024 John Wiley & Sons Ltd.)

Pancreatic ductal adenocarcinoma (PDAC) has earned a notorious reputation as one of the most formidable and deadliest malignant tumors. Within the tumor microenvironment, cancer cells have acquired the capability to maintain incessant expansion and increased proliferation in response to hypoxia via metabolic reconfiguration, leading to elevated levels of lactate within the tumor surroundings. However, there have been limited studies specifically investigating the association between hypoxia and lactic acid metabolism-related lactylation in PDAC. In this study, multiple machine learning approaches, including LASSO regression analysis, XGBoost, and Random Forest, were employed to identify hub genes and construct a prognostic risk signature. The implementation of the CERES score and single-cell analysis was used to discern a prospective therapeutic target for the management of PDAC. CCK8 assay, colony formation assays, transwell, and wound-healing assays were used to explore both the proliferation and migration of PDAC cells affected by CENPA . In conclusion, we discovered two distinct subtypes characterized by their unique hypoxia and lactylation profiles and developed a risk score to evaluate prognosis, as well as response to immunotherapy and chemotherapy, in PDAC patients. Furthermore, we indicated that CENPA may serve as a promising therapeutic target for PDAC.

Compound drought-heatwaves (CDHWs) accelerate the warming and drying of soils, triggering soil compound drought-heatwaves (SCDHWs) that jeopardize the health of soil ecosystems. Nevertheless, the behavior of these events worldwide and their responses to climatic warming are underexplored. Here, we show a global escalation in the frequency, duration, peak intensity, and severity of SCDHWs, as well as an increase in affected land area, from 1980 to 2023. The increasing trends, which are particularly prominent since the early 2000 s, and projected to persist throughout this century, are dominated by summertime SCDHWs and enhanced by El Niño. Intensive soil warming as well as climatologically lower soil temperatures compared to air temperatures lead to localized hotspots of escalating SCDHW severity in northern high latitudes, while prolonged duration causes such hotspots in northern South America. Transformation of natural ecosystems, particularly forests and wetlands, to cropland as well as forest degradation substantially enhance the strength of SCDHWs. Global SCDHWs consistently exhibit higher frequencies, longer durations, greater severities, and faster growth rates than CDHWs in all aspects from 1980 to 2023. They are undergoing a critical transition, with droughts replacing heatwaves as the primary constraint. We emphasize the significant intensification of SCDHWs in northern high latitudes as well as the prolonged duration of SCDHWs in the Southern Hemisphere, posing an underrated threat to achieving carbon neutrality and food security goals., Competing Interests: Competing interests statement:The authors declare no competing interest.

Antibiotic resistance resulting from the overuse of antibiotics sets a high challenge for brutal antimicrobial treatment. Although photothermal therapy (PTT) overcomes the awkward situation of antibiotic resistance, it usually mistakenly kills the beneficial bacteria strains when eliminating pernicious bacteria. Specifically recognizing and damaging the target pathogens is urgently required for PTT-mediated sterilization strategy. Based on the host-guest recognition between cucurbit[10]uril (CB[10]) and porphyrins, two water-soluble supramolecular porphyrins are designed and implement selective bactericidal effect via in situ bacteria-responsive near-infrared (NIR) PTT. With the help of CB[10], the π-π stacking and hydrophobic interactions of porphyrins are efficiently inhibited, thus contributing to a good photostability and a high photothermal conversion efficiency. Attributing to the matching reduction potential between facultative anaerobic Escherichia coli (E. coli) and porphyrins, they are selectively in situ reduced into supramolecular phlorin and supramolecular chlorin by E. coli, successfully achieving a selective sterilization against E. coli. In vivo, the in situ bacteria-responsive NIR PTT systems also promote the quick recovery of E. coli-infected abscesses and trauma on mice without inducing obvious systemic toxicity, providing a new alternative to the current antibiotics and helping relieve the global public health crisis of abusive antibiotics., (© 2024 Wiley‐VCH GmbH.)

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.

Natural polyphenols, abundant in the human diet, are derived from a wide variety of sources. Numerous preclinical studies have demonstrated their significant anticancer properties against various malignancies, making them valuable resources for drug development. However, traditional experimental methods for developing anticancer therapies from natural polyphenols are time-consuming and labor-intensive. Recently, artificial intelligence has shown promising advancements in drug discovery. Integrating AI technologies into the development process for natural polyphenols can substantially reduce development time and enhance efficiency. In this study, we review the crucial roles of natural polyphenols in anticancer treatment and explore the potential of AI technologies to aid in drug development. Specifically, we discuss the application of AI in key stages such as drug structure prediction, virtual drug screening, prediction of biological activity, and drug-target protein interaction, highlighting the potential to revolutionize the development of natural polyphenol-based anticancer therapies., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest related to this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Our work presents a novel spectrum-inspired learning-based approach for generating clothing deformations with dynamic effects and personalized details. Existing methods in the field of clothing animation are limited to either static behavior or specific network models for individual garments, which hinders their applicability in real-world scenarios where diverse animated garments are required. Our proposed method overcomes these limitations by providing a unified framework that predicts dynamic behavior for different garments with arbitrary topology and looseness, resulting in versatile and realistic deformations. First, we observe that the problem of bias towards low frequency always hampers supervised learning and leads to overly smooth deformations. To address this issue, we introduce a frequency-control strategy from a spectral perspective that enhances the generation of high-frequency details of the deformation. In addition, to make the network highly generalizable and able to learn various clothing deformations effectively, we propose a spectral descriptor to achieve a generalized description of the global shape information. Building on the above strategies, we develop a dynamic clothing deformation estimator that integrates graph attention mechanisms with long short-term memory. The estimator takes as input expressive features from garments and human bodies, allowing it to automatically output continuous deformations for diverse clothing types, independent of mesh topology or vertex count. Finally, we present a neural collision handling method to further enhance the realism of garments. Our experimental results demonstrate the effectiveness of our approach on a variety of free-swinging garments and its superiority over state-of-the-art methods.

Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m 6 A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage., Competing Interests: Declaration of competing interest The authors declare no competing financial and/or non-financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sepsis, a life-threatening condition resulting in multiple organ dysfunction, is characterized by a dysregulated immune response to infection. Current treatment options are limited, leading to unsatisfactory outcomes for septic patients. Here, we present a series of studies utilizing compact bone mesenchymal stem cells (CB-MSCs) and their derived paracrine mediators, especially exosome (CB-MSCs-Exo), to treat mice with cecal ligation and puncture-induced sepsis. Our results demonstrate that CB-MSCs treatment significantly improves the survival rate of septic mice by mitigating excessive inflammatory response and attenuating sepsis-induced organ injuries. Furthermore, CB-MSCs-conditioned medium, CB-MSCs secretome (CB-MSCs-Sec), and CB-MSCs-Exo exhibit potent anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated murine macrophage (RAW264.7). Intriguingly, intravenous administration of CB-MSCs-Exo confers superior protection against inflammation and organ damage in septic mice compared to CB-MSCs in certain aspects. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomic analysis, we identify a range of characterized proteins derived from the paracrine activity of CB-MSCs, involved in critical biological processes such as immunomodulation and apoptosis. Our findings highlight that the paracrine products of CB-MSCs could serve as a promising cell-free therapeutic agent for sepsis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oncidium hybridum Lodd. is an important ornamental flower that is used as both a cut flower and a potted plant around the world; additionally, its pseudobulbs serve as essential carriers for floral organs and flower development. The NAM gene family is crucial for managing responses to various stresses as well as regulating growth in plants. However, the mechanisms by which NAM genes regulate the development of pseudobulbs remain unclear. In this study, a total of 144 NAM genes harboring complete structural domains were identified in O. hybridum . The 144 NAM genes were systematically classified into 14 distinct subfamilies via phylogenetic analysis. Delving deeper into the conserved motifs revealed that motifs 1-6 exhibited remarkable conservation, while motifs 7-10 presented in a few NAM genes only. Notably, NAM genes sharing identical specific motifs were classified into the same subfamily, indicating functional relatedness. Furthermore, the examination of occurrences of gene duplication indicated that the NAM genes display 16 pairs of tandem duplications along with five pairs of segmental duplications, suggesting their role in genetic diversity and potential adaptive evolution. By conducting a correlation analysis integrating transcriptomics and metabolomics at four stages of pseudobulb development, we found that OhNAM023 , OhNAM030 , OhNAM007 , OhNAM019 , OhNAM083 , OhNAM047 , OhNAM089 , and OhNAM025 exhibited significant relationships with the endogenous plant hormones jasmonates (JAs), hinting at their potential involvement in hormonal signaling. Additionally, OhNAM089 , OhNAM025 , OhNAM119 , OhNAM055 , and OhNAM136 showed strong links with abscisic acid (ABA) and abscisic acid glucose ester (ABA-GE), suggesting the possible regulatory function of these NAM genes in plant growth and stress responses. The 144 NAM genes identified in this study provide a basis for subsequent research and contribute to elucidating the intricate molecular mechanisms of NAM genes in Oncidium and potentially in other species.

Plants generate a range of physiological and molecular responses to sustain their growth and development when suffering heat stress. Avocado is a type of tropical fruit tree with high economic value. Most avocado cultivars delete, wither, or even die when exposed to heat stress for a long time, which seriously restricts the introduction and cultivation of avocados. In this study, samples of a heat-intolerant variety (' Hass ') were treated under heat stress, and the transcriptomics and metabolomics were analyzed, with the expectation of providing information on the variety improvement and domestication of avocados. The differentially expressed genes identified using transcriptome analysis mainly involved metabolic pathways such as plant hormone signal transduction, plant-pathogen interaction, and protein processing in the endoplasmic reticulum. Combined transcriptome and metabolome analysis indicated that the down-regulation of Hass.g03.10206 and Hass.g03.10205 in heat shock-like proteins may result in the reduced Trehalose and Sinapoyl aldehyde content. Metabolomics analysis results indicated that the decrease in Trehalose and Sinapoyl aldehyde content may be an important factor for heat intolerance. These results provide important clues for understanding the physiological mechanisms of adaptation to heat stress in avocados.

Oat ( Avena sativa L.) is an annual grass that has a high nutritional value and therapeutic benefits. β-glucan is one of the most important nutrients in oats. In this study, we investigated two oat varieties with significant differences in β-glucan content (high β-glucan oat varieties BY and low β-glucan content oat variety DY) during different filling stages. We also studied the transcriptome sequencing of seeds at different filling stages. β-glucan accumulation was highest at days 6-16 in the filling stage. Differentially expressed genes (DEGs) were selected from the dataset of transcriptome sequencing. Among them, three metabolic pathways were closely related to the biosynthesis of β-glucan by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, including xyloglucan:xyloglucosyl transferase activity, starch and sucrose metabolism, and photosynthesis. By analyzing the expression patterns of DEGs, we identified one CslF2 gene and 32 transcription factors. Five modules were thought to be positively correlated with β-glucan accumulation by weighted gene co-expression network analysis (WGCNA). Moreover, the expression levels of candidate genes obtained from the transcriptome sequencing were further validated by quantitative real-time PCR (RT-qPCR) analysis. Our study provides a novel way to identify the regulatory mechanism of β-glucan synthesis and accumulation in oat seeds and offers a possible pathway for the genetic engineering of oat breeding for higher-quality seeds., Competing Interests: The authors declare there are no competing interests., (©2024 Qi et al.)

Fusarium mycotoxins are of great concern because they are the most common food-borne mycotoxins and environmental contaminants worldwide. Fusaric acid (FA), Deoxynivalenol (DON), Zearalenone (ZEA), T-2 toxin (T-2), and Fumonisin B1 (FB1) are important Fusarium toxins contaminating feeds and food and can cause serious health problems. FA can synergize with some other Fusarium toxins to enhance overall toxicity. However, the underlying molecular mechanism remains poorly understood. In this study, our CRISPR screening revealed Malate dehydrogenase 2 (MDH2) and Pyruvate dehydrogenase E1 subunit beta (PDHB) are the key genes for FA-induced cell death. Pathways associated with mitochondrial function, notably the TCA cycle, play a significant role in FA cytotoxicity. We found that MDH2 and PDHB depletion reduced FA-induced cell death, ROS accumulation, and the expression of caspase-3 and HIF-1α. The cell viability assays and flow cytometry demonstrated that MDH2 knockout but not PDHB decreased DON, ZEA, T-2, and FB1-induced cytotoxicity, apoptosis, and ROS accumulation. MDH2 inhibitor LW6 also decreased DON, ZEA, T-2, and FB1-induced toxicity. This suggested that MDH2, but not PDHB, is a common regulator of broad-spectrum Fusarium toxin (FA, DON, ZEA, T-2, and FB1)-induced cell death. Our work provides new avenues for the treatment of Fusarium toxin toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enzymatic reaction-mediated microbial transformation has emerged as a promising technology with significant potential in various industries. These technologies offer the ability to produce enzymes on a large scale, optimize their functionality, and enable sustainable production processes. By utilizing microbial hosts and manipulating their genetic makeup, enzymes can be synthesized efficiently and tailored to meet specific industrial requirements. This leads to enhanced enzyme performance and selectivity, facilitating the development of novel processes and the production of valuable compounds. Moreover, microbial transformation and biosynthesis offer sustainable alternatives to traditional chemical methods, reducing environmental impact and promoting greener production practices. Microbial transformations enrich drug candidate diversity and enhance active ingredient potency, benefiting the pharmaceutical industry. Continued advancements in genetic engineering and bioprocess optimization drive further innovation and application development in Enzymatic reaction-mediated microbial transformation. The integration of AI for predicting enzymatic reactions and optimizing pathways marks a promising direction for future research. In summary, these technologies have the potential to revolutionize several industries by providing cost-effective, sustainable solutions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Objective: To explore the link between plasma aldosterone concentration (PAC) and the prevalence of metabolic dysfunction-related fatty liver disease (MAFLD) in hypertensive patients., Methods: We analyzed data from 41,131 hospitalized patients from January 1, 2014, to December 31, 2023. Multivariate logistic regression models tested associations, with threshold, subgroup, and sensitivity analyses conducted to validate findings., Results: For each 5-unit increase in PAC, the risk of MAFLD rose by 1.57 times, consistent even in the fully adjusted model. The odds ratios for the Q2, Q3, and Q4 groups compared to Q1 were 1.21, 2.12, and 3.14, respectively. A threshold effect was observed at 14 ng/dL, with subgroup and sensitivity analyses supporting these results., Conclusions: This study reveals a significant positive association between elevated PAC levels and the prevalence of MAFLD in hypertensive patients. These findings underscore the imperative for further large-scale, prospective studies to validate and expand upon this correlation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shen, Cai, Hu, Song, Zhu, Ma, Zhang, Ma, Zhou, Yang, Hong, Zhang and Li.)

High-entropy alloys (HEAs) present both significant potential and challenges for developing efficient electrocatalysts due to their diverse combinations and compositions. Here, we propose a procedural approach that combines high-throughput experimentation with data-driven strategies to accelerate the discovery of efficient HEA electrocatalysts for the hydrogen evolution reaction (HER). This enables the rapid preparation of HEA arrays with various element combinations and composition ratios within a model system. The intrinsic activity of the HEA arrays is swiftly screened using scanning electrochemical cell microscopy (SECCM), providing precise composition-activity data sets for the HEA system. An ensemble machine learning (EML) model is then used to predict the activity database for the composition subspace of the system. Based on these database results, two groups of promising catalysts are recommended and validated through actual electrocatalytic evaluations. This procedural approach, which combines high-throughput experimentation with data-driven strategies, provides a new pathway to accelerate the discovery of efficient HEA electrocatalysts.

China's sustained air quality improvement is hindered by unregulated ammonia (NH 3 ) emissions from inefficient nitrogen management in smallholder farming. Although the Chinese government is promoting a policy shift to large-scale farming, the benefits of this, when integrated with nitrogen management, remain unclear. Here we fill this gap using an integrated assessment, by combining geostatistical analysis, high-resolution emission inventories, farm surveys and air quality modeling. Smallholder-dominated farming allows only 13%-31% NH 3 reduction, leading to limited PM 2.5 decreases nationally due to non-linear PM 2.5 chemistry. Conversely, large-scale farming would double nitrogen management adoption rates, increasing NH 3 reduction potential to 48%-58% and decreasing PM 2.5 by 9.4-14.0 μg·m -3 in polluted regions. The estimated PM 2.5 reduction is conservative due to localized NH 3 -rich conditions under large-scale livestock farming. This strategy could prevent over 300 000 premature deaths and achieve a net benefit of US $68.4-86.8 billion annually, unlocking immense benefits for air quality and agricultural sustainability., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Staphylococcus aureus is a notorious pathogen predominantly involved in skin and soft tissue infections, exhibiting a distinct innate sex bias. This study explores the influence of testosterone on the virulence of S. aureus and elucidates its underlying mechanisms. Utilizing a skin abscess model in intact and castrated male mice, we assessed the effects of testosterone on S. aureus pathogenicity. Compared to controls, castrated mice showed significantly reduced abscess sizes and decreased bacterial loads, highlighting the role of testosterone in modulating the severity of S. aureus infections. In vitro experiments revealed that testosterone enhances the hemolytic activity, cytotoxicity, and oxidative stress resistance of S. aureus. Real-time quantitative PCR analysis showed a significant upregulation of the genes encoding α-hemolysin (hla) and phenol-soluble modulin (psmα). Importantly, testosterone treatment significantly enhanced the expression of the accessory gene regulator (Agr) quorum-sensing system components (agrC, agrA, agrB, agrD), while the SaeRS system (saeR, saeS, and sbi) exhibited only slight changes. Gene knockout experiments revealed that deletion of agrC, rather than saeRS and agrBD, abolishes the testosterone-induced enhancement of hemolysis and gene expression, underscoring the key role of AgrC. Molecular docking simulations indicated a direct interaction between testosterone and AgrC protein, with a strong binding affinity at the active site residue SER201. This study provides new insights into the mechanistic basis of how testosterone enhances the pathogenicity of S. aureus, potentially contributing to increased male susceptibility to S. aureus infections and offering a targeted approach for therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although CA19-9 is an essential blood biomarker of pancreatic cancer (PC), its sensitivity and specificity are limited for early detection., Methods: We analyzed the serum proprotein convertase subtilisin/kexin type 9 (sPCSK9) in PC patients, benign disease groups (BDG), and healthy controls (HC) by ELISA., Results: Consistently, sPCSK9 was considerably lower in PC patients than in HC (Z = -2.546, P < 0.05), and sPCSK9 in PC patients was statistically significantly higher than in BDG (Z = -5.457, P < 0.001). sPCSK9 was linked to the invasion of lymph nodes (χ 2 = 6.846, P < 0.01). According to ROC curves, combining sPCSK9 with CA19-9 could potentially enhance the diagnostic capability of CA19-9 in early-stage PC patients. Furthermore, the low sPCSK9 group ( n = 41) exhibited statistically significantly prolonged overall survival compared to the high sPCSK9 group ( n = 15), with median survival times of 27 months (95% CI [17.59-36.41]) and 11 months (95% CI [7.21-14.79]), respectively ( P = 0.022)., Conclusion: The diagnostic performance of CA19-9 for early-stage PC patients could be improved by combining sPCSK9 with CA19-9. Moreover, the higher sPCSK9 group has a significantly shorter overall survival rate., Competing Interests: The authors declare that they have no competing interests., (© 2024 Xu et al.)

Minimizing cadmium (Cd) contamination in rice grains is crucial for ensuring food security and promoting sustainable agriculture. Utilizing genetic modification to generate rice varieties with low Cd accumulation is a promising strategy due to its cost-effectiveness and operational simplicity. Our study demonstrated that the CRISPR-Cas9-mediated quadruple mutation of the multicopper oxidase genes OsLPR1/3/4/5 in the japonica rice cultivar Tongjing 981 had little effect on yields. However, a notable increase was observed in the cell wall functional groups that bind with Cd. As a result, the quadruple mutation of OsLPR1/3/4/5 enhanced Cd sequestration within the cell wall while reducing Cd concentrations in both xylem and phloem sap, thereby inhibiting Cd transport from roots to shoots. Consequently, Cd concentrations in brown rice and husk in oslpr1/3/4/5 quadruple mutants (qm) decreased by 52% and 55%, respectively, compared to the wild-type. These findings illustrate that the quadruple mutation of OsLPR1/3/4/5 is an effective method for minimizing Cd contamination in rice grains without compromising yields. Therefore, the quadruple mutation of OsLPR1/3/4/5 via biotechnological pathways may represent a valuable strategy for the generation of new rice varieties with low Cd accumulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or astrocyte-specific Acss1 deletion to elevate acetate levels, we observed mitigated metabolic and cognitive impairments in SF mice. Mechanistically, acetate binds and activates pyruvate carboxylase, thereby restoring glycolysis and the tricarboxylic acid cycle. Among individuals most commonly affected by SF, patients with obstructive sleep apnea exhibited elevated acetate levels when coupled with type 2 diabetes. Our study uncovers the protective effect of acetate against sleep-induced metabolic and cognitive impairments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nucleotide-binding leucine-rich repeat (NLR) proteins are crucial intracellular immune receptors in plants, responsible for detecting invading pathogens and initiating defense responses. While previous studies on the evolution and function of NLR genes were mainly limited to land plants, the evolutionary trajectory and immune-activating character of NLR genes in algae remain less explored. In this study, genome-wide NLR gene analysis was conducted on 44 chlorophyte species across seven classes and seven charophyte species across five classes. A few but variable number of NLR genes, ranging from one to 20, were identified in five chlorophytes and three charophytes, whereas no NLR gene was identified from the remaining algal genomes. Compared with land plants, algal genomes possess fewer or usually no NLR genes, implying that the expansion of NLR genes in land plants can be attributed to their adaptation to the more complex terrestrial pathogen environments. Through phylogenetic analysis, domain composition analysis, and conserved motifs profiling of the NBS domain, we detected shared and lineage-specific features between NLR genes in algae and land plants, supporting the common origin and continuous evolution of green plant NLR genes. Immune-activation assays revealed that both TNL and RNL proteins from green algae can elicit hypersensitive responses in Nicotiana benthamiana, indicating the molecular basis for immune activation has emerged in the early evolutionary stage of different types of NLR proteins. In summary, the results from this study suggest that NLR proteins may have taken a role as intracellular immune receptors in the common ancestor of green plants., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Objective: Depression and insomnia frequently co-occur, but the neural mechanisms between patients with varying degrees of these conditions are not fully understood. The specific topological features and connectivity patterns of this co-morbidity have not been extensively studied. This study aimed to investigate the topological characteristics of topological characteristics and functional connectivity of brain networks in depressed patients with insomnia., Methods: Resting-state functional magnetic resonance imaging data from 32 depressed patients with a high level of insomnia (D-HI), 35 depressed patients with a low level of insomnia (D-LI), and 81 healthy controls (HC) were used to investigate alterations in brain topological organization functional networks. Nodal and global properties were analyzed using graph-theoretic techniques, and network-based statistical analysis was employed to identify changes in brain network functional connectivity., Results: Compared to the HC group, both the D-HI and D-LI groups showed an increase in the global efficiency (Eglob) values, local efficiency (Eloc) was decreased in the D-HI group, and Lambda and shortest path length (Lp) values were decreased in the D-LI group. At the nodal level, the right parietal nodal clustering coefficient (NCp) values were reduced in D-HI and D-LI groups compared to those in HC. The functional connectivity of brain networks in patients with D-HI mainly involves default mode network (DMN)-cingulo-opercular network (CON), DMN-visual network (VN), DMN-sensorimotor network (SMN), and DMN-cerebellar network (CN), while that in patients with D-LI mainly involves SMN-CON, SMN-SMN, SMN-VN, and SMN-CN. The values of the connection between the midinsula and postoccipital gyrus was negatively correlated with scores for early awakening in D-HI., Conclusion: These findings may contribute to our understanding of the underlying neuropsychological mechanisms in depressed patients with insomnia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Nutritional support has been identified as a potential intervention for cognitive frailty; however, the association between 25-hydroxyvitamin D [25-(OH)D], vitamin B12, and cognitive frailty remains ambiguous., Methods: This study utilized data from two cycles (2011-2012, 2013-2014) of the National Health and Nutrition Examination Survey (NHANES) to investigate this relationship. The researchers constructed a 41-item frailty index encompassing diverse aspects of physical functioning, psychological evaluation, and medical conditions, and evaluated each participant individually. The study utilized Spearman's rank correlation coefficient and univariate ordered logistic regression to assess the relationships between variables and cognitive frailty. Recursive feature elimination and cross-validation methods were employed to identify the most influential variables for building and optimizing multivariate ordered logistic regression models. Subgroup analyses and interaction tests were further conducted to validate the identified correlations., Results: The findings of this study confirm a negative linear correlation between 25-(OH)D levels and cognitive frailty in older adults. Specifically, a one-unit increase in 25-(OH)D levels was associated with a 12% reduction in the risk of cognitive frailty. The result was further supported by subgroup analyses and interaction tests., Conclusion: The existence of a negatively correlated linear association between 25-(OH)D levels and cognitive frailty in older adults is plausible, but further rigorously designed longitudinal studies are necessary to validate this relationship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Tang, Yang, Feng, Yuan, Jiang, Hu and Dong.)

Background: Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs., Methods: Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant., Results: Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death., Conclusions: Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance., Competing Interests: Potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Gastric cancer-related morbidity and mortality rates are high in China. Patients who have undergone gastric cancer surgery should receive six cycles of chemotherapy according to their condition. During this period, intestinal obstruction is likely to occur. Electrolyte balance disorders, peritonitis, intestinal necrosis, and even hypovolemic shock and septic shock can seriously affect the physical and mental recovery of patients and threaten their health and quality of life (QoL)., Aim: To quantitatively explore the effects of enhanced recovery after surgery (ERAS)-based nursing on anxiety, depression, and QoL of elderly patients with postoperative intestinal obstruction after gastric cancer., Methods: The clinical data of 129 older patients with intestinal obstruction after gastric cancer surgery who were treated and cared for in our hospital between January 2019 and December 2021 were examined retrospectively. Nine patients dropped out because of transfer, relocation, or death . According to the order of admissions, the patients were categorized into either a comparison group or an observation group according to the random number table, with 60 cases in each group., Results: After nursing care, the observation group required significantly less time to eat for the first time, recover bowel sounds, pass gas, and defecate than the comparison group ( P < 0.05). No significant difference was noted in nutrition-related indicators between the two groups before care. Before care, the Symptom Check List-90 scores between the two groups were comparable, whereas anxiety, depression, paranoia, fear, hostility, obsession, somatization, interpersonal sensitivity, and psychotic scores were significantly lower in the observation group after care ( P < 0.05). The QoL scores between the two groups before care did not differ significantly. After care, the physical, social, physiological, and emotional function scores; mental health score; vitality score; and general health score were significantly higher in the observation group, whereas the somatic pain score was significantly lower in the observation group ( P < 0.05)., Conclusion: ERAS-based nursing combined with conventional nursing interventions can effectively improve patient's QoL, negative emotions, and nutritional status; accelerate the time to first ventilation; and promote intestinal function recovery in elderly patients with postoperative intestinal obstruction after gastric cancer surgery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes., Design and Methods: This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes., Results: A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules., Conclusions: PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The separation and purification of chemical raw materials, particularly neutral compounds with similar physical and chemical properties, represents an ongoing challenge. In this study, we introduce a class of water-soluble macrocycle compound, calix[2]azolium[2]benzimidazolone (H), comprising two azolium and two benzimidazolone subunits. The heterocycle subunits form a hydrophobic binding pocket that enables H1 to encapsulate a series of neutral guests in water with 1:1 or 2:1 stoichiometry, including aldehydes, ketones, and nitrile compounds. The host-guest complexation in the solid state was further confirmed through X-ray crystallography. Remarkably, H1 was shown to be a nonporous adaptive crystal material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid states. This work not only demonstrates that azolium-based macrocycles are promising candidates for the encapsulation of organic molecules but also shows the potential application in separation science., (© 2024. The Author(s).)

Effective nitrogen fertilizer management is crucial for reducing nitrous oxide (N 2 O) emissions while ensuring food security within planetary boundaries. However, climate change might also interact with management practices to alter N 2 O emission and emission factors (EFs), adding further uncertainties to estimating mitigation potentials. Here, we developed a new hybrid modeling framework that integrates a machine learning model with an ensemble of eight process-based models to project EFs under different climate and nitrogen policy scenarios. Our findings reveal that EFs are dynamically modulated by environmental changes, including climate, soil properties, and nitrogen management practices. Under low-ambition nitrogen regulation policies, EF would increase from 1.18%-1.22% in 2010 to 1.27%-1.34% by 2050, representing a relative increase of 4.4%-11.4% and exceeding the IPCC tier-1 EF of 1%. This trend is particularly pronounced in tropical and subtropical regions with high nitrogen inputs, where EFs could increase by 0.14%-0.35% (relative increase of 11.9%-17%). In contrast, high-ambition policies have the potential to mitigate the increases in EF caused by climate change, possibly leading to slight decreases in EFs. Furthermore, our results demonstrate that global EFs are expected to continue rising due to warming and regional drying-wetting cycles, even in the absence of changes in nitrogen management practices. This asymmetrical influence of nitrogen fertilizers on EFs, driven by climate change, underscores the urgent need for immediate N 2 O emission reductions and further assessments of mitigation potentials. This hybrid modeling framework offers a computationally efficient approach to projecting future N 2 O emissions across various climate, soil, and nitrogen management scenarios, facilitating socio-economic assessments and policy-making efforts., (© 2024 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Aging induces a series of alterations, specifically a decline in the stature and number of villi and crypts in the small intestine, thus compromising the absorbent capability of the villi. This investigation employed a senolytic combination of dasatinib and quercetin (D+Q) to examine its impact on the intestinal tract of elderly mice. Our findings demonstrate that D+Q treatment leads to a decrease in the expression of p21, p16, and Ki67, while concurrently triggering removal of apoptotic cells within the villi. Additionally, D+Q treatment exhibits the ability to promote growth in both the height and quantity of villi and crypts, along with stimulating nitric oxide (NO) production in aged mice. The study presented a model to assess strategies to alleviate age-related senescence in the intestinal tract of elderly mice. Importantly, D+Q showcases promising potential in enhancing intestinal functionality within the aging.

Objective: White matter lesions (WMLs) increase the risk of stroke, stroke recurrence, and death. Higher plasma aldosterone concentration (PAC) increases the risk of stroke, acute myocardial infarction, and hypertension. The objective is to evaluate the relationship between PAC and cerebrovascular events in patients with hypertension and WMLs., Methods: We conducted a retrospective cohort study that included 1041 participants hospitalized. The outcome was new-onset cerebrovascular events including intracerebral hemorrhage and stroke. A Cox regression model was used to evaluate the relationship between baseline PAC and the risk of cerebrovascular events., Results: The mean age of participants was 60.9 ± 10.2 years and 565 (53.4%) were males. The median follow-up duration was 42 months (interquartile range: 25-67), and 92 patients experienced new-onset cerebrovascular events. In a multivariate-adjusted model, with PAC as a continuous variable, higher PAC increased the risk of cerebrovascular events; patient risk increased per 1 (hazard ratio [HR: 1.03], 95% confidence interval [CI]: 1.01-1.06, P < .01), per 5 (HR: 1.17, 95% CI: 1.06-1.31, P < .01), and per 10 ng/dL (HR: 1.41, 95%: 1.14-1.75, P < .01) increase in PAC. When PAC was expressed as a categorical variable (quartile: Q1-Q4), patients in Q4 (HR: 2.12, 95% CI: 1.18-3.79, P < .05) exhibited an increased risk of cerebrovascular events compared to Q1. Restrictive spline regression showed a linear association between PAC and the risk of new-onset cerebrovascular events after adjusting for all possible variables., Conclusions: Our study identified a linear association between PAC and the risk of new-onset cerebrovascular events in patients with hypertension and WMLs., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Within the poultry industry, hens' reproductive performance is of great economic significance. The development and growth of follicles is a key aspect of hen egg production, and ovarian follicle growth and development are closely associated with granulosa cells (GCs) proliferation and the synthesis of steroid hormones. It has been confirmed by numerous studies that microRNAs (miRNAs) play important roles in the steroid hormone synthesis and proliferation of GCs. In this study, we examined the main miRNAs influencing hens' ability to reproduce, identified the miR-223 that is mainly expressed in atretic follicles based on sequencing, and investigated its role in GCs. Then, we used miR-223 mimic and inhibitor to knockdown or overexpress miR-223 expression. The result showed that miR-223 significantly inhibits both the steroid hormone synthesis and the proliferation of GCs. Subsequently, the results of the dual luciferase reporter experiment and bioinformatics prediction demonstrated that cysteine rich transmembrane BMP regulator 1 (CRIM1) was a downstream target gene of miR-223, and overexpression of miR-223 prevented CRIM1 expression. The function of CRIM1 was further investigated, and we observed a significant reduction in the synthesis of steroid hormones and the proliferation of GCs after transfection with CRIM1 siRNA. The opposite function of miR-223 was observed for CRIM1 in our study. Additionally, we demonstrated the involvement of the miR-223/CRIM1 axis in GCs through modulation of the AKT signaling pathway. Our data demonstrate the pivotal role of the miR-223 in the proliferation and steroid hormone synthesis of chicken GCs, which helps to explain how non-coding RNA (ncRNA) affects chicken reproductive function., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Anthropogenic activities have substantially enhanced the loadings of reactive nitrogen (Nr) in the Earth system since pre-industrial times 1,2 , contributing to widespread eutrophication and air pollution 3-6 . Increased Nr can also influence global climate through a variety of effects on atmospheric and land processes but the cumulative net climate effect is yet to be unravelled. Here we show that anthropogenic Nr causes a net negative direct radiative forcing of -0.34 [-0.20, -0.50] W m -2 in the year 2019 relative to the year 1850. This net cooling effect is the result of increased aerosol loading, reduced methane lifetime and increased terrestrial carbon sequestration associated with increases in anthropogenic Nr, which are not offset by the warming effects of enhanced atmospheric nitrous oxide and ozone. Future predictions using three representative scenarios show that this cooling effect may be weakened primarily as a result of reduced aerosol loading and increased lifetime of methane, whereas in particular N 2 O-induced warming will probably continue to increase under all scenarios. Our results indicate that future reductions in anthropogenic Nr to achieve environmental protection goals need to be accompanied by enhanced efforts to reduce anthropogenic greenhouse gas emissions to achieve climate change mitigation in line with the Paris Agreement., (© 2024. The Author(s).)