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Abstract Constrained by the AC voltage amplitude modulated by a modular multilevel converter‐based static synchronous compensator (MMC‐STATCOM), its reactive power output may be subject to oscillations under grid contingencies, posing a threat to the grid stable operation. To solve this problem, this paper proposes a variable DC voltage (VDCV)‐based reactive power enhancement scheme for MMC‐STATCOM. In this scheme, a novel variable DC voltage control is designed, which can increase the DC voltage in a transient state for relaxing the constraint of the AC voltage amplitude modulated by MMC‐STATCOM and improving its reactive power output capability (RPC). At the same time, to make full use of the improved RPC of MMC‐STATCOM, a VDCV scheme also proposes an optimisation algorithm of its reactive current‐AC voltage droop coefficient using the established reactive power model of the MMC‐STATCOM. Based on small signal modelling and analysis, the key parameters of the proposed VDCV scheme are optimised. The performance and reactive power enhancement of the VDCV scheme is evaluated through the hardware‐in‐the‐loop experiment under grid disturbances.

Abstract Fluxes in human copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate. We herein apply an unbiased temporal evaluation of the signaling and whole genome transcriptional activities modulated by copper level fluctuations to identify potential copper sensor proteins responsible for driving these activities. We find that fluctuations in physiologically relevant copper levels modulate EGFR signal transduction and activation of the transcription factor CREB. Both intracellular and extracellular assays support Cu1+ inhibition of the EGFR phosphatase PTPN2 (and potentially PTPN1)–via ligation to the PTPN2 active site cysteine side chain–as the underlying mechanism. We additionally show i) copper supplementation drives weak transcriptional repression of the copper importer CTR1 and ii) CREB activity is inversely correlated with CTR1 expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper stimulated EGFR/CREB signaling and CTR1 expression.

Abstract Cis-regulatory elements (CREs) are pivotal in orchestrating gene expression throughout diverse biological systems. Accurate identification and in-depth characterization of functional CREs are crucial for decoding gene regulation networks during cellular processes. In this study, we develop Kethoxal-Assisted Single-stranded DNA Assay for Transposase-Accessible Chromatin with Sequencing (KAS-ATAC-seq) to quantitatively analyze the transcriptional activity of CREs. A main advantage of KAS-ATAC-seq lies in its precise measurement of ssDNA levels within both proximal and distal ATAC-seq peaks, enabling the identification of transcriptional regulatory sequences. This feature is particularly adept at defining Single-Stranded Transcribing Enhancers (SSTEs). SSTEs are highly enriched with nascent RNAs and specific transcription factors (TFs) binding sites that define cellular identity. Moreover, KAS-ATAC-seq provides a detailed characterization and functional implications of various SSTE subtypes. Our analysis of CREs during mouse neural differentiation demonstrates that KAS-ATAC-seq can effectively identify immediate-early activated CREs in response to retinoic acid (RA) treatment. Our findings indicate that KAS-ATAC-seq provides more precise annotation of functional CREs in transcription. Future applications of KAS-ATAC-seq would help elucidate the intricate dynamics of gene regulation in diverse biological processes.

Abstract Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

Abstract Chimeric antigen receptor (CAR) T cells show suboptimal efficacy in acute myeloid leukemia (AML). We find that CAR T cells exposed to myeloid leukemia show impaired activation and cytolytic function, accompanied by impaired antigen receptor downstream calcium, ZAP70, ERK, and C-JUN signaling, compared to those exposed to B-cell leukemia. These defects are caused in part by the high expression of CD155 by AML. Overexpressing C-JUN, but not other antigen receptor downstream components, maximally restores anti-tumor function. C-JUN overexpression increases costimulatory molecules and cytokines through reinvigoration of ERK or transcriptional activation, independent of anti-exhaustion. We conduct an open-label, non-randomized, single-arm, phase I trial of C-JUN-overexpressing CAR-T in AML (NCT04835519) with safety and efficacy as primary and secondary endpoints, respectively. Of the four patients treated, one has grade 4 (dose-limiting toxicity) and three have grade 1–2 cytokine release syndrome. Two patients have no detectable bone marrow blasts and one patient has blast reduction after treatment. Thus, overexpressing C-JUN endows CAR-T efficacy in AML.

Abstract Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

Abstract Dry reforming of methane (DRM) is a highly endothermic process, with its development hindered by the harsh thermocatalytic conditions required. We propose an innovative DRM approach utilizing a 16 W pulsed laser in combination with a cost-effective Mo2C catalyst, enabling DRM under milder conditions. The pulsed laser serves a dual function by inducing localized high temperatures and generating *CH plasma on the Mo2C surface. This activates CH4 and CO2, significantly accelerating the DRM reaction. Notably, the laser directly generates *CH plasma from CH4 through thermionic emission and cascade ionization, bypassing the traditional step-by-step dehydrogenation process and eliminating the rate-limiting step of methane cracking. This method maintains a carbon-oxygen balanced environment, thus preventing the deactivation of the Mo2C catalyst due to CO2 oxidation. The laser-catalytic DRM achieves high yields of H2 (14300.8 mmol h−1 g−1) and CO (14949.9 mmol h−1 g−1) with satisfactory energy efficiency (0.98 mmol kJ−1), providing a promising alternative for high-energy-consuming catalytic systems.

Abstract The demand for larger and lighter mechanisms for next-generation space missions necessitates using deployable structures. High-strain fiber polymer composites show considerable promise for such applications due to their exceptional strength-to-weight ratio, manufacturing versatility, packaging efficiency, and capacity for self-deployment using stored strain energy. However, a significant challenge in using composite deployable structures for space applications arises from the unavoidable extended stowage periods before they are deployed into their operational configuration in orbit. During the stowage period, the polymers within the composites experience material degradation due to their inherent viscoelastic and/or plastic properties, causing stress relaxation and accumulation of plastic strains, thereby reducing the deployment capability and resulting in issues related to recovery accuracy. This paper aims to give a state-of-the-art review of recent advances in the design, modeling, and manufacturing of high-strain composites for deployable structures in space applications, emphasizing the long-term stowage effects. This review is intended to initiate discussion of future research to enable efficient, robust, and accurate design of composite deployable structures that account for the enduring challenges posed by long-term stowage effects.

Abstract Urate, the physiological form of uric acid and a potent antioxidant in serum, plays a pivotal role in scavenging reactive oxygen species. Yet excessive accumulation of urate, known as hyperuricemia, is the primary risk factor for the development of gout. The high-capacity urate transporter GLUT9 represents a promising target for gout treatment. Here, we present cryo-electron microscopy structures of human GLUT9 in complex with urate or its inhibitor apigenin at overall resolutions of 3.5 Å and 3.3 Å, respectively. In both structures, GLUT9 exhibits an inward open conformation, wherein the substrate binding pocket faces the intracellular side. These structures unveil the molecular basis for GLUT9’s substrate preference of urate over glucose, and show that apigenin acts as a competitive inhibitor by occupying the substrate binding site. Our findings provide critical information for the development of specific inhibitors targeting GLUT9 as potential therapeutics for gout and hyperuricemia.

Objective Thoracic spinal epidural abscess (SEA) is a rare but dangerous condition, and traditional surgical methods are accompanied by extensive trauma and approach‐related complications. Here we introduce the technique of full‐endoscopic transforaminal debridement and decompression and evaluate its feasibility for treating brucellar thoracic SEA. Methods We performed thoracic full‐endoscopic transforaminal decompression and debridement on two patients with neurological deficits caused by brucellar SEA, which is mainly composed of granulation tissue rather than pus. Postoperative MRI was conducted to confirm the presence of any residual abscess compressing the nerves. Frankel grading was employed to assess the recovery of neurological function, and complications were documented. Results There were no occurrences of dural tear, postoperative hematoma, or pulmonary complications. Their neurological function had significantly improved after surgery, and postoperative MRI confirmed no residual abscess compressing the spinal cord. During the 2‐year follow‐up, one patient achieved complete recovery (from Frankel‐C to Frankel‐E), while another patient improved from Frankel‐A to Frankel‐D. Neither patient experienced infection recurrence, instability, nor kyphotic deformity. Conclusion We described the novel application of transforaminal endoscopic surgery in brucellar thoracic granulomatous SEA and preliminarily indicated the feasibility of this technique as a minimally invasive alternative to open surgery.

Abstract The degradation of earthen sites due to natural and human factors has become a pressing issue, necessitating urgent protection measures. In this context, accurate assessment of the vulnerability of earthen sites is essential for the development of effective conservation strategies. In this study, a comprehensive evaluation framework that incorporates multiple indicators is proposed. In particular, the entropy weight- (Technique for Order Preference by Similarity to an Ideal Solution) TOPSIS method is employed for quantitative vulnerability assessment and combined with K-means clustering to define vulnerability levels for earthen sites. To validate the proposed approach, the vulnerability of 29 sections of the Ming Great Wall is evaluated. Eventually, the 29 earthen sites are categorized into three levels: high, medium, and low, according to their degree of vulnerability. The results of gray correlation analysis and entropy weight-TOPSIS method are compared using the ontology missing amount in the original data as the validation standard. The results show that the Pearson correlation coefficient value of the entropy weight-TOPSIS method with the ontology missing amount was 0.859, while the Pearson correlation coefficient value of the gray correlation analysis method with the ontology missing amount was 0.691, so that the results of the entropy weight-TOPSIS method can more accurately reflect the actual vulnerability of earthen sites.

Abstract Osteophytes are frequently observed in elderly people and most commonly appear at the anterior edge of the cervical and lumbar vertebrae body. The anterior osteophytes keep developing and will lead to neck/back pain over time. In clinical practice, the accurate measurement of the anterior osteophyte length and the understanding of the temporal progression of anterior osteophyte growth are of vital importance to clinicians for effective treatment planning. This study proposes a new measuring method using the osteophyte ratio index to quantify anterior osteophyte length based on lateral radiographs. Moreover, we develop a continuous stochastic degradation model with time-related functions to characterize the anterior osteophyte formation and growth process on cervical and lumbar vertebrae over time. Follow-up data of anterior osteophytes up to 9 years are obtained for measurement and model validation. The agreement test indicates excellent reproducibility for our measuring method. The proposed model accurately fits the osteophyte growth paths. The model predicts the mean time to onset of pain and obtained survival function of the degenerative vertebrae. This research opens the door to future quantification and mathematical modeling of the anterior osteophyte growth on human cervical and lumbar vertebrae. The measured follow-up data is shared for future studies.

Abstract Background Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with poor prognosis. Further mechanistic insights into the molecular mechanisms of CCA are needed to develop more effective target therapy. Methods The expression of the histone lysine acetyltransferase KAT2B in human CCA was analyzed in human CCA tissues. CCA xenograft was developed by inoculation of human CCA cells with or without KAT2B overexpression into SCID mice. Western blotting, ChIP-qPCR, qRT-PCR, protein immunoprecipitation, GST pull-down and RNA-seq were performed to delineate KAT2B mechanisms of action in CCA. Results We identified KAT2B as a frequently downregulated histone acetyltransferase in human CCA. Downregulation of KAT2B was significantly associated with CCA disease progression and poor prognosis of CCA patients. The reduction of KAT2B expression in human CCA was attributed to gene copy number loss. In experimental systems, we demonstrated that overexpression of KAT2B suppressed CCA cell proliferation and colony formation in vitro and inhibits CCA growth in mice. Mechanistically, forced overexpression of KAT2B enhanced the expression of the tumor suppressor gene NF2, which is independent of its histone acetyltransferase activity. We showed that KAT2B was recruited to the promoter region of the NF2 gene via interaction with the transcription factor SP1, which led to enhanced transcription of the NF2 gene. KAT2B-induced NF2 resulted in subsequent inhibition of YAP activity, as reflected by reduced nuclear accumulation of oncogenic YAP and inhibition of YAP downstream genes. Depletion of NF2 was able to reverse KAT2B-induced reduction of nuclear YAP and subvert KAT2B-induced inhibition of CCA cell growth. Conclusions This study provides the first evidence for an important tumor inhibitory effect of KAT2B in CCA through regulation of NF2-YAP signaling and suggests that this signaling cascade may be therapeutically targeted for CCA treatment.

Abstract Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer—which are believed to be connected to the malfunction of multigene and multilevel cell signaling network—remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

In this study, the mesoporous material NCNT was prepared by treating carbon nanotubes (CNT) with hydrazine and subsequently loaded with Cu-Fe layered double hydroxide (CuFeLDH) to create a multiphase catalyst (CuFeLDH-NCNT). Its application as a multiphase catalyst was investigated in an ultrasound-assisted Fenton process for ciprofloxacin (CIP) degradation in aqueous solution. In addition, the impacts of catalyst dosage, ultrasonic power, H2O2 dosage, and beginning pH on CIP removal efficiency were carefully evaluated to maximize the removal efficiency of CIP. The findings indicated that the elimination rate of the initial CIP concentration of 20 mg/L surpassed 94.66% after a mere 100 min, while the TOC degradation rate was 70.4%. The high removal rate was due to the synergistic action between the nanoparticles, H2O2, and ultrasonography. The degradation intermediates of CIP were examined, and putative degradation pathways and mechanisms were postulated. HIGHLIGHTS Preparation of CuFeLDH–NCNT material as an efficient catalyst for ultrasound-assisted Fenton-like reaction.; Enhanced catalytic performance of H2O2 by the synergistic effect of CuFeLDH–NCNT.; Effective degradation of CIP by CuFeLDH–NCNT/US/H2O2.; Good stability and reusability of CuFeLDH–NCNT, with a low metal leaching rate.;

This paper comprehensively reviews the application and research progress of CO2 fracturing fluids in China, highlights the existing issues and puts forward suggestions for future development. Three types of fracturing fluid systems containing CO2, namely, CO2 dry fracturing fluid, CO2 energized fracturing fluid, and CO2 foam fracturing fluid, are categorized based on the mass ratio and process difference between CO2, water, and treatment agents. Field applications in China reveal several problem to be resolved: (1) The application scope of CO2 fracturing fluids is restricted to depleted reservoirs, re-fracturing of old wells, and medium-deep reservoirs with low formation pressure coefficients; (2) different types of CO2 fracturing fluids require different processes and ground supporting equipment; (3) optimization of CO2 compatibility, functionality, temperature and salt tolerance, as well as the cost of treatment agents is necessitated; (4) existing CO2 fracturing fluid system fail to perform well with low friction, low filtration, and high sand-carrying capacity. (5) there lacks a targeted industry standard for evaluation of performance of CO2 fracturing fluid system and treatment agents. Therefore, in order to meet the goals of CCUS-EOR, CCUS-EGR, or integration of fracturing, displacement and burial by CO2, efforts should be made in the aspects that followed, including in-depth investigation of the mechanism of CO2 fracturing fluids, the adaptability and compatibility between existing equipment, different CO2 fracturing fluid systems and processes, and construction of treatment agents, low-density proppants and high-performance systems of recyclability and industrial-grade. In addition, optimization of CO2 fracturing fluid system based fracturing design is also crucial taking such related factors such as overall reservoir geological conditions, petrophysical properties, CO2 transportation, and well site layout into consideration.

Abstract The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the β-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-βAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

Abstract The placenta is a unique organ for ensuring normal embryonic growth in the uterine. Here, we found that maternal RNA transcription in Dlk1-Dio3 imprinted domain is essential for placentation. PolyA signals were inserted into Gtl2 to establish a mouse model to prevent the expression of maternal RNAs in the domain. The maternal allele knock-in (MKI) and homozygous (HOMO) placentas showed an expanded junctional zone, reduced labyrinth and poor vasculature impacting both fetal and maternal blood spaces. The MKI and HOMO models displayed dysregulated gene expression in the Dlk1-Dio3 domain. In situ hybridization detected Dlk1, Gtl2, Rtl1, miR-127 and Rian dysregulated in the labyrinth vasculature. MKI and HOMO induced Dlk1 to lose imprinting, and DNA methylation changes of IG-DMR and Gtl2-DMR, leading to abnormal gene expression, while the above changes didn’t occur in paternal allele knock-in placentas. These findings demonstrate that maternal RNAs in the Dlk1-Dio3 domain are involved in placental vasculature, regulating gene expression, imprinting status and DNA methylation.

Background and aimsThe role of dietary factors in metabolic dysfunction-associated steatotic liver disease (MASLD)—which represents a new definition of liver steatosis and metabolic dysfunction— remains unclear. This study aimed to explore the relationships between dietary indices and MASLD.MethodsWe analyzed data from the United States National Health and Nutrition Examination Survey (NHANES) 2017–2020 cycle, including 4,690 participants with complete vibration-controlled transient elastography (VCTE) data. Multivariate logistic regression models adjusted for covariates were used to assess the association between dietary indices, MASLD, and MASLD-associated liver fibrosis (MASLD-LF). Restricted cubic spline (RCS) models and subgroup analyses were also performed.ResultsThe Alternative Healthy Eating Index (AHEI), Healthy Eating Index-2020 (HEI-2020), Dietary Approaches to Stop Hypertension Index (DASHI), and Mediterranean Diet Index (MEDI) were found to be negatively associated with MASLD risk, while the Dietary Inflammatory Index (DII) had a positive association. The highest quartile of MEDI was linked to a 44% reduction in MASLD risk [Q1 vs. Q4 odds ratio (OR): 0.56; 95% confidence interval (CI): 0.34–0.94, P for trend: 0.012]. DASHI was uniquely associated with a reduced risk of MASLD-LF (continuous OR: 0.79; 95% CI: 0.64–0.97; p for trend: 0.003). Our RCS curves indicated a nonlinear association with DASHI-MASLD (p-overall: 0.0001, p-nonlinear: 0.0066). Subgroup analyses showed robust associations among the non-Hispanic White and highly educated populations.ConclusionSpecific dietary patterns were associated with reduced risks of MASLD and MASLD-LF. The DASHI, in particular, showed a significant protective effect against MASLD-LF. These findings suggest potential dietary interventions for managing MASLD and MASLD-LF, although large-scale randomized controlled trials are warranted to validate these findings.

Introduction: Long-term imaging of live cells is commonly used for the study of dynamic cell behaviors. It is crucial to keep the cell viability during the investigation of physiological and biological processes by live cell imaging. Conventional incubators that providing stable temperature, carbon dioxide (CO2) concentration, and humidity are often incompatible with most imaging tools. Available commercial or custom-made stage-top incubators are bulky or unable to provide constant environmental conditions during long time culture.Methods: In this study, we reported the development of the microscope incubation system (MIS) that can be easily adapted to any inverted microscope stage. Incremental PID control algorithm was introduced to keep stable temperature and gas concentration of the system. Moreover, efficient translucent materials were applied for the top and bottom of the incubator which make it possible for images taken during culture.Results: The MIS could support cell viability comparable to standard incubators. When used in real time imaging, the MIS was able to trace single cell migration in scratch assay, T cell mediated tumor cells killing in co-culture assay, inflation-collapse and fusion of organoids in 3D culture. And the viability and drug responses of cells cultured in the MIS were able to be calculated by a label-free methods based on long term imaging.Discussion: We offer new insights into monitoring cell behaviors during long term culture by using the stage adapted MIS. This study illustrates that the newly developed MIS is a viable solution for long-term imaging during in vitro cell culture and demonstrates its potential in cell biology, cancer biology and drug discovery research where long-term real-time recording is required.

ObjectiveDietary factors and nutritional status may be among the risk factors for Chronic Obstructive Pulmonary Disease (COPD). There exists a certain correlation between trace elements and COPD. Through Mendelian Randomization (MR) analysis, we investigated the causal relationships between trace elements, inflammatory proteins, and COPD.MethodsWe employed MR, multivariable MR (MVMR), and two-step MR (TSMR) approaches to assess the causal links between 15 trace elements and COPD, with 91 inflammatory proteins serving as mediators to further elucidate the tripartite causal relationships.ResultsTrace elements such as Folate (OR = 1.293, 95%CI 1.027–1.628; p = 0.029), Vitamin D (OR = 1.331, 95%CI 1.071–1.654; p = 0.010), Vitamin B12 (OR = 1.424, 95%CI 1.108–1.828; p = 0.006), and Iron (OR = 0.741, 95%CI 0.580–0.946; p = 0.016) demonstrated causal relationships with COPD. No causal relationship was observed in reverse MR. After adjusting for BMI, Folate (OR = 1.633, 95%CI 1.098–2.429; p = 0.015), Iron (OR = 0.507, 95%CI 0.31–0.778; p = 0.001), and Vitamin D (OR = 1.511, 95%CI 1.029–2.217; p = 0.034) were identified as independent risk factors for COPD, whereas Vitamin B12 (OR = 1.118, 95%CI 0.751–1.666; p = 0.581) was not. Mediation analysis indicated that CDCP1 (5.76%) may play a mediating role between Iron and COPD.ConclusionTrace elements such as Folate, Vitamin D, Vitamin B12, and Iron have causal relationships with COPD. After BMI adjustment, Folate, Vitamin D, and Iron emerge as independent risk factors. Furthermore, the inflammatory protein CDCP1 may partially mediate the causal relationship between Iron and COPD, offering a scientific basis for dietary recommendations that could benefit COPD patients. The supplementation of trace elements may be advantageous for individuals suffering from COPD.

BackgroundThe prevalence of venous thromboembolism (VTE) is high in patients with cancer and can often present as the first symptom of malignancy. Cancer-associated VTE is one of the most important risk factors contributing to cancer mortality, making its prevention and treatment critical for patients with lung cancer.MethodsWe systematically searched for observational studies that estimated the prevalence of VTE in patients with lung cancer. A comprehensive search of electronic databases, including PubMed, EMBASE and Cochrane Library, was systematically conducted from database inception through January 21, 2022. The qualities of included studies were assessed in three domains, including patient selection, comparison, and results. Random effects meta-analyses of the prevalence of VTE in lung cancer were conducted using the metaprop procedure. Chi-square test and I2 value were used to evaluate study heterogeneity.ResultsThirty-five studies involving 742,156 patients were considered eligible for this study. The pooled prevalence of VTE among patients with lung cancer was 5% (95% CI: 0.043–0.056, P = 0.000). The regional prevalence of VTE was 7% (95% CI: 0.06–0.08; I2 = 99.2%) in North America, 8% (95% CI: 0.06–0.10; I2 = 97.6%) in Asia, 6% (95% CI: 0.04–0.09; I2 = 95.9%) in Europe and 11% (95% CI: 0.07–0.15) in Australasia.ConclusionsThe prevalence of lung cancer-related VTE is high and region-specific. These results of this review emphasize the importance of understanding the incidence of lung cancer-related VTE and provide argue for VTE screening of patients with lung cancer.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022306400).

The carbon dioxide reduction reaction (CO2RR) is one of the most promising solutions for realizing carbon neutralization via converting the emitted CO2 into value‐added chemicals. The CC coupling step for CO dimerization is the rate‐determining step for C2 pathways, which have not been thoroughly investigated. Herein, the direct cation stabilization effects on CO dimerization for *OCCO formation on the representative Cu(100) and Pt(100) surfaces are investigated. Density functional theory calculations show that the presence of alkali metal ions plays a vital role in promoting the coupling of *CO monomers on both metal surfaces, where Cu shows a stronger stabilization effect. More importantly, a strong linear correlation (R2 ≈ 0.9) between the dimer stabilization energy and the reaction energy is revealed for the first time, which is a promising indicator for the selectivity of C2 pathways. Further investigations on electronic structures reveal that the promoting effect on *OCCO formation is strongly related to the negative charges of the molecules, in which the negative charge accumulation is favored by the directional electron transfer due to the chemisorption of *OCCO on Cu(100) surface. This work offers insights into the understanding of CC coupling reactions for CO2RR mechanisms.

When a strong earthquake occurs, roads are the lifelines of rescue. The rapid development of high-resolution satellite imaging platforms has made the application of remote sensing technology for road damage identification possible. Over the years, road damage identification has required a significant amount of manual involvement, making it difficult to meet the needs of rapid post-disaster response. The automatic recognition of road damage using satellite images has always been difficult. Damaged areas appear in the satellite images with blurry boundaries, versatile sizes, and uneven spatial distributions. With the aim of automatic pixel-level road damage identification, we introduce the first road damage dataset, CAU-RoadDamage, which includes high-resolution satellite images and pixel-level human annotations. Moreover, we propose the application of a pre-trained vision foundation model for the first time to automatically identify road damage. Low-rank adaptation technology is used to fine-tune the foundation model on the satellite images, and two-way attention is used to integrate the foundation model with domain specialist model components. The proposed segmentation model is compared to multiple state-of-the-art methods on the CAU-RoadDamage dataset. Our approach achieves the highest F1 of 76.09%, which is notably higher than that of the other models. The experimental results demonstrate the feasibility of pixel-level road damage recognition and the applicability of vision foundation models for downstream remote sensing tasks. The CAU-RoadDamage dataset will be made publicly available at https://github.com/CAU-HE/RoadDamageExtraction.

Lavender, an aromatic plant with a history dating back to ancient Egypt and Greece, is consumed because of its diverse pharmacological properties, including sedation, sleep aid, and antidepressant effects. However, the mechanisms underlying these antidepressant properties remain unclear. In this study, we explored the impact of lavender essential oil (LEO) inhalation on the diversity of gut microbiota, metabolites, and differential gene expression in the hippocampus of alcohol-withdrawn depressive rats. Additionally, we examined alterations in the hippocampal transient receptor potential (TRP) channel-mediated inflammatory regulation within the brain-gut axis of depressive rats. The results demonstrated a significant decrease in sucrose preference, diminished activity in the central zone of the open field test, and prolonged immobility time in the forced swim test in alcohol-withdrawn depressive rats, indicating the amelioration of depressive states following lavender essential oil inhalation. 16 S rDNA sequencing analysis revealed a significant reduction in Bacteroidota and Muribaculaceae in the gut of alcohol-withdrawn depressive rats, whereas lavender essential oil significantly increased the relative abundance of Muribaculaceae and other bacterial species. Metabolomic analysis identified 646 distinct metabolites as highly correlated biomarkers between the model and lavender essential oil groups. Furthermore, lavender essential oil inhalation significantly attenuated hippocampal inflammatory factors IL-2, IL-6, IL-1β, and TNF-α. This study identified elevated expression of Trpv4 and Calml4 in the hippocampal region of alcohol-withdrawn depressed rats and showed that lavender essential oil inhalation regulated aberrantly expressed genes. Our research suggests that lavender essential oil downregulates Trpv4, modulates inflammatory factors, and alleviates depressive-like behavior in alcohol withdrawal rats.

In this paper, a direct cooling pipe for hydrogen inside the marine hydrogen storage cylinder (HSC) was designed, and the cooling pipe was simulated and analyzed under different cooling structures and different cooling fluids using ANSYS(Fluent) 2022 R2. The simulation results show that the effect of different cooling fluids on the temperatures were nearly the same. The heat transfer coefficients, however, of various fluids were different, and the cooling temperature was also different after cooling for the same time. The cooling structures mainly affect the cooling rate of the hydrogen due to the contact area with hydrogen inside the HSC. Among the three structures investigated in this study, the cooling capacity of the spiral layout was increased by 0.85 % and 0.63 %, respectively, compared to the rectangular and wavy layout. The rectangular layout has the certain cooling effect, however, in comparison to the spiral tube structure, it has too many corners, which increases the hindering effect on the flow of cooling medium inside the tubes and affects the cooling efficiency. The wavy layout has the largest contact area, but it has the problems of uneven cooling and occupying a large amount of hydrogen storage space. Among the three structures, comprehensively speaking, the spiral layout is considered to be the optimal. The optimal performance parameters were determined by comparing the simulation results of the three layouts during cooling process with hydrogen charging being performed. The results show that the cooling pipe can achieve the hydrogen temperature to be controlled within 358 K before the hydrogen pressure in the HSC reaches 70 MPa, and the maximum temperature is 336.07 K was obtained after the completion of hydrogen filling. This paper gives technical information for optimizing the thermal performance and safety of the hydrogen fueling system.

Abstract Background In December 2022, a large‐scale epidemic occurred in China due to Omicron variant of SARS‐CoV‐2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS‐CoV‐2 Omicron infection among recipients of allo‐HSCT. Methods This single‐center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. Results The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1–65 years), with the male‐to‐female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non‐Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p

Abstract Microbial factories lacking the ability of dynamically regulating the pathway enzymes overexpression, according to in situ metabolite concentrations, are suboptimal, especially when the metabolic intermediates are competed by growth and chemical production. The production of higher alcohols (HAs), which hijacks the amino acids (AAs) from protein biosynthesis, minimizes the intracellular concentration of AAs and thus inhibits the host growth. To balance the resource allocation and maintain stable AA flux, this work utilizes AA‐responsive transcriptional attenuator ivbL and HA‐responsive transcriptional activator BmoR to establish a concentration recognition‐based auto‐dynamic regulation system (CRUISE). This system ultimately maintains the intracellular homeostasis of AA and maximizes the production of HA. It is demonstrated that ivbL‐driven enzymes overexpression can dynamically regulate the AA‐to‐HA conversion while BmoR‐driven enzymes overexpression can accelerate the AA biosynthesis during the HA production in a feedback activation mode. The AA flux in biosynthesis and conversion pathways is balanced via the intracellular AA concentration, which is vice versa stabilized by the competition between AA biosynthesis and conversion. The CRUISE, further aided by scaffold‐based self‐assembly, enables 40.4 g L−1 of isobutanol production in a bioreactor. Taken together, CRUISE realizes robust HA production and sheds new light on the dynamic flux control during the process of chemical production.

Advancements in tissue engineering are crucial for successfully healing tendon-bone connections, especially in situations like anterior cruciate ligament (ACL) restoration. This study presents a new and innovative three-dimensional scaffold, reinforced with nanofibers, that is specifically intended for acellular tendon complexes. The scaffold consists of a distinct layered arrangement comprising an acellular tendon core, a middle layer of polyurethane/type I collagen (PU/Col I) yarn, and an outside layer of poly (L-lactic acid)/bioactive glass (PLLA/BG) nanofiber membrane. Every layer is designed to fulfill specific yet harmonious purposes. The acellular tendon core is a solid structural base and a favorable environment for tendon cell functions, resulting in considerable tensile strength. The central PU/Col I yarn layer is vital in promoting the tendinogenic differentiation of stem cells derived from tendons and increasing the expression of critical tendinogenic factors. The external PLLA/BG nanofiber membrane fosters the process of bone marrow mesenchymal stem cells differentiating into bone cells and enhances the expression of markers associated with bone formation. Our scaffold's biocompatibility and multi-functional design were confirmed through extensive in vivo evaluations, such as histological staining and biomechanical analyses. These assessments combined showed notable enhancements in ACL repair and healing. This study emphasizes the promise of multi-layered nanofiber scaffolds in orthopedic tissue engineering and also introduces new possibilities for the creation of improved materials for regenerating the tendon-bone interface.

Waste pollution poses a significant threat to the survival of wildlife. In particular, microplastic pollution has received widespread attention. However, data on the exposure of threatened wildlife in nature conservation to microplastics, a very valuable basic data for animal conservation, are still limited. This study was conducted in the Qinling Mts., a key biodiversity hotspot and an essential genetic resource repository in China. Over the span from 2021 to 2023, a total of 22 fecal samples were collected from three species with different feeding habits over four months in two nature reserves in the Qinling Mts.: takin (Budorcas taxicolor), leopard cat (Prionailurus bengalensis), and golden snub-nosed monkey (Rhinopithecus roxellana). The potential reasons influencing the content of microplastics were studied on the basis of the distance of the fecal samples from the nearest residential area. Laser Direct Infrared Spectroscopy identified 34 types of microplastics, with diameters ranging from 20 to 100 μm. Among them, acrylate copolymer, polyethylene, and polyurethane were the main types. Leopard cat (67.06 particles/g d.w.) had a significantly higher microplastic content than the takins (20.53 particles/g d.w.; Z=-3.162, P=0.002) and golden snub-nosed monkeys (27.69 particles/g d.w.; Z=-2.193, P=0.028). The average microplastic content in leopard cats and takins exhibited a negative correlation with the distance from residential areas. In conclusion, our study demonstrates the presence of microplastics within threatened terrestrial wildlife. Addressing this pressing issue may require concerted efforts to reduce plastic consumption in the surrounding regions, which could help mitigate the adverse impacts on wildlife.

Abstract Background Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear. Results Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis. Conclusions Together, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces’ RPSA.

The massive use of antibiotics has led to the aggravation of bacterial resistance and also brought environmental pollution problems. This poses a great threat to human health. If the dosage of antibiotics is reduced by increasing its bactericidal performance, the emergence of drug resistance is certainly delayed, so that there's not enough time for developing drug resistance during treatment. Therefore, we selected typical representative materials of metal Ag and semiconductor ZnO nano-bactericides to design and synthesize Ag/ZnO hollow core–shell structures (AZ for short). Antibiotics are grafted on the surface of AZ through rational modification to form a composite sterilization system. The research results show that the antibacterial efficiency of the composite system is significantly increased, from the sum (34.7% + 22.8% = 57.5%) of the antibacterial efficiency of AZ and gentamicin to 80.2%, net synergizes 22.7%, which fully reflects the effect of 1 + 1 > 2. Therefore, the dosage of antibiotics can be drastically reduced in this way, which makes both the possibility of bacterial resistance and medical expenses remarkably decrease. Subsequently, residual antibiotics can be degraded under simple illumination using AZ-self as a photocatalyst, which cuts off the path of environmental pollution. In short, such an innovative route has guiding significance for drug resistance.

This paper presents the design of a novel multi-beam Luneburg lens antenna with specific dielectric structure and proposes a new solution for downsizing planar lens antennas. The quasi-conformal transformation optics (QCTO) principle is applied to achieve an equivalent transformation relation between the spatial coordinate and the electromagnetic properties of material, effectively preserving the behavior of electromagnetic waves while achieving a significant reduction in antenna size. The antenna comprises a deformed Luneburg lens with a radius equivalent to $3.75\lambda $ , metal plates flanking the lens, and a linear array of seven microstrip antennas operating at 10 GHz. By selectively activating antenna elements within the array, the antenna can generate seven distinct beams, enabling a scanning range of ±30° in the azimuth plane. Each beam achieves a gain exceeding 15 dBi. In comparison to traditional planar lens antennas, this antenna boasts a reduction in size of more than 30% and has the flexibility of being fed using a linear array.

Infrared small target detection is critical to infrared search and tracking systems. However, accurate and robust detection remains challenging due to the scarcity of target information and the complexity of clutter interference. Existing methods have some limitations in feature representation, leading to poor detection performance in complex scenes. Especially when there are sharp edges near the target or in cluster multitarget detection, the “target suppression” phenomenon tends to occur. To address this issue, we propose a robust unsupervised multifeature representation (RUMFR) method for infrared small target detection. On the one hand, robust unsupervised spatial clustering (RUSC) is designed to improve the accuracy of feature extraction; on the other hand, pixel-level multiple feature representation is proposed to fully utilize the target detail information. Specifically, we first propose the center-weighted interclass difference measure (CWIDM) with a trilayer design for fast candidate target extraction. Note that CWIDM also guides the parameter settings of RUSC. Then, the RUSC-based model is constructed to accurately extract target features in complex scenes. By designing the parameter adaptive strategy and iterative clustering strategy, RUSC can robustly segment cluster multitargets from complex backgrounds. Finally, RUMFR that fuses pixel-level contrast, distribution, and directional gradient features is proposed for better target representation and clutter suppression. Extensive experimental results show that our method has stronger feature representation capability and achieves better detection performance than several state-of-the-art methods.

The output of new energy represented by wind power and photovoltaic power features volatility and randomness. It is a practical approach to use the guaranteed rate with statistical characteristics to analyze the output coefficient of new energy. However, there is a lack of analysis and demonstration on the value of the new energy output guaranteed rate. To solve this problem, a selection method for the new energy output guaranteed rate considering optimal energy storage configuration is proposed. First, the influence of the new energy output guaranteed rate on the new energy output coefficient is analyzed. Secondly, with the goal of minimizing the comprehensive costs, an optimal configuration model of energy storage based on the output guaranteed rate of new energy is constructed, and particle swarm optimization is used for the optimization solution. Then, according to the optimal energy storage configuration results under different guaranteed rates, a reasonable new energy output guaranteed rate is determined by maximizing the comprehensive benefits obtained from energy storage. Finally, an example applied to the power grid in an area of Guangdong in Southern China is provided to illustrate the effectiveness of the proposed method.

Prunus tongmuensis, a new species of cherry blossom, is described and illustrated from Wuyishan National Park, southeast China. This species is characterized by its tubular to nearly bottle-shaped receptacles and dark purple drupes. It can be distinguished from other wild cherry trees by its flowers and leaves, reddish brown young leaves, presence of 1–2 glands at the base of leaves, petioles densely covered with yellowish brown villi, longer pedicels (0.6–2.5 cm), villous pistil, and dark purple drupes. In the present study, we conducted a comprehensive morphological study based on specimens of the new species and its morphologically close species, field observations, and examination of pollen morphology. In addition, our phylogenetic analysis based on the complete plastid genome sequences further confirms the status of the new species and indicates that it is closely related to Prunus clarofolia, however, it notably differs in leaf shape, size, petiole villus color, gland location, timing of flower and leaf openings, and reflexed or spread sepals, as well as drupe color.

Abstract Background Spodoptera litura is a harmful pest that feeds on more than 80 species of plants, and can be infected and killed by Spodoptera litura nucleopolyhedrovirus (SpltNPV). SpltNPV-C3 is a type C SpltNPV clone, that was observed and collected in Japan. Compared with type A or type B SpltNPVs, SpltNPV-C3 can cause the rapid mortality of S. litura larvae. Methods In this study, occlusion bodies (OBs) and occlusion-derived viruses (ODVs) of SpltNPV-C3 were purified, and OBs were observed by scanning electron microscopy (SEM). ODVs were observed under a transmission electron microscope (TEM). Results Both OBs and ODVs exhibit morphological characteristics typical of nucleopolyhedroviruses (NPVs).The genome of SpltNPV-C3 was sequenced and analyzed; the total length was 148,634 bp (GenBank accession 780,426,which was submitted as SpltNPV-II), with a G + C content of 45%. A total of 149 predicted ORFs were found. A phylogenetic tree of 90 baculoviruses was constructed based on core baculovirus genes. LC‒MS/MS was used to analyze the proteins of SpltNPV-C3; 34 proteins were found in the purified ODVs, 15 of which were core proteins. The structure of the complexes formed by per os infectivity factors 1, 2, 3 and 4 (PIF-1, PIF-2, PIF-3 and PIF-4) was predicted with the help of the AlphaFold multimer tool and predicted conserved sequences in PIF-3. SpltNPV-C3 is a valuable species because of its virulence, and the analysis of its genome and proteins in this research will be beneficial for pest control efforts.

Abstract One-carbon (C1) substrates, such as methanol or formate, are attractive feedstocks for circular bioeconomy. These substrates are typically converted into formaldehyde, serving as the entry point into metabolism. Here, we design an erythrulose monophosphate (EuMP) cycle for formaldehyde assimilation, leveraging a promiscuous dihydroxyacetone phosphate dependent aldolase as key enzyme. In silico modeling reveals that the cycle is highly energy-efficient, holding the potential for high bioproduct yields. Dissecting the EuMP into four modules, we use a stepwise strategy to demonstrate in vivo feasibility of the modules in E. coli sensor strains with sarcosine as formaldehyde source. From adaptive laboratory evolution for module integration, we identify key mutations enabling the accommodation of the EuMP reactions with endogenous metabolism. Overall, our study demonstrates the proof-of-concept for a highly efficient, new-to-nature formaldehyde assimilation pathway, opening a way for the development of a methylotrophic platform for a C1-fueled bioeconomy in the future.

Abstract Comprehensively understanding the female reproductive system is crucial for safeguarding fertility and preventing diseases concerning women's health. With the capacity to simulate the intricate physio- and patho-conditions, and provide diagnostic platforms, microfluidic chips have fundamentally transformed the knowledge and management of female reproductive health, which will ultimately promote the development of more effective assisted reproductive technologies, treatments, and drug screening approaches. This review elucidates diverse microfluidic systems in mimicking the ovary, fallopian tube, uterus, placenta and cervix, and we delve into the culture of follicles and oocytes, gametes’ manipulation, cryopreservation, and permeability especially. We investigate the role of microfluidics in endometriosis and hysteromyoma, and explore their applications in ovarian cancer, endometrial cancer and cervical cancer. At last, the current status of assisted reproductive technology and integrated microfluidic devices are introduced briefly. Through delineating the multifarious advantages and challenges of the microfluidic technology, we chart a definitive course for future research in the woman health field. As the microfluidic technology continues to evolve and advance, it holds great promise for revolutionizing the diagnosis and treatment of female reproductive health issues, thus propelling us into a future where we can ultimately optimize the overall wellbeing and health of women everywhere. Graphical Abstract

Abstract Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. Methods A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. Results Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. Conclusions These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.

With the massive participation of new energy in the operation of distribution network (DN), the uncertainties arising from both load and renewable generation have brought challenges to its secure and reliable operation. In this paper, a model of day-ahead and intraday optimal scheduling based on dynamic partitioning (DP) of DN is constructed to realize the refinement of operation in both temporal and spatial dimensions, as well as to improve the reliability of system operation. For the strong fluctuation characteristics of the source-load in DN, the DP is achieved under the premise that the partition structure in each period is tight and the internal power supply has the ability to balance the power fluctuations. In order to improve the regional autonomy of DN, a day-ahead multi-objective optimal scheduling model is constructed based on the DP with the optimization objectives of weak inter-partition power coupling, lowest deficiency rate of flexibility, and lowest operating cost. And a scheme for articulation is proposed to ensure the effective guidance of day-ahead for intraday. Then the intraday dispatch model is constructed by shifting the focus to the incorporate characteristics of DP and quickly smooth the net load fluctuations. Finally, the performance and reliability of the proposed models are verified via case studies.

Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.

Wind erosion increases risks to soil productivity and food security, which have large implications for ecosystems and human well-being. However, the spatial patterns of how ecological restoration and climate change affect wind erosion remain poorly understood. Here, we combined scenario analysis with wind erosion assessment to evaluate the spatial associations of wind erosion with ecological restoration and climatic factors on the Tibetan Plateau. A structural equation model (SEM) was developed to determine the major driver of wind erosion. We identified an overall decrease of wind erosion modulus during 2001–2018, followed by increases of 7.2–19.4% under different climate change scenarios in 2030. Nearly two-thirds of the study area was characterized by wind erosion primarily driven by climate change, while ecological restoration accounted for the wind erosion in almost two-fifths of the study area. The SEM revealed a dominating role played by wind speed in affecting wind erosion directly and indirectly by modulating soil and vegetation conditions. Our study highlights the importance of embracing the spatial variations in the impacts of ecological restoration and climatic factors into the systematic planning of soil conservation and management. Results of this study could inform response strategies aiming to prevent and control wind erosion by identifying the location and extent of affected ecosystem services in the context of climate change.

Objectives To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting.Methods This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m2 at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months.Results Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p

ObjectiveThis study employed Mendelian Randomization (MR) to investigate the causal relationships among immune cells, COPD, and potential metabolic mediators.MethodsUtilizing summary data from genome-wide association studies, we analyzed 731 immune cell phenotypes, 1,400 plasma metabolites, and COPD. Bidirectional MR analysis was conducted to explore the causal links between immune cells and COPD, complemented by two-step mediation analysis and multivariable MR to identify potential mediating metabolites.ResultsCausal relationships were identified between 41 immune cell phenotypes and COPD, with 6 exhibiting reverse causality. Additionally, 21 metabolites were causally related to COPD. Through two-step MR and multivariable MR analyses, 8 cell phenotypes were found to have causal relationships with COPD mediated by 8 plasma metabolites (including one unidentified), with 1-methylnicotinamide levels showing the highest mediation proportion at 26.4%.ConclusionWe have identified causal relationships between 8 immune cell phenotypes and COPD, mediated by 8 metabolites. These findings contribute to the screening of individuals at high risk for COPD and offer insights into early prevention and the precocious diagnosis of Pre-COPD.

Background: Hypertension is a prevalent condition with significant impacts on human health. Chinese herbal foot bath, a traditional Chinese medicine treatment, is believed to help manage hypertension. Objective: This systematic review aims to assess the efficacy of combining Chinese herbal foot bath with conventional treatment for hypertension. Methods: A thorough search across eight databases was conducted to identify relevant studies on Chinese herbal foot bath for hypertension. Randomized controlled trials examining the benefits and risks of using Chinese herbal foot bath combined with conventional treatment for hypertension were included. Blood pressure changes before and after the Chinese herbal foot bath were assessed, and outcomes were analyzed using Review Manager 5.3 software. The certainty of evidence was evaluated using the GRADE tool. Results: Compared to conventional treatment, Chinese herbal foot bath combined with conventional treatment demonstrated greater effectiveness in reducing systolic blood pressure (MD 6.69, 95% CI: 5.86 to 7.53, p

BackgroundLow-intensity pulsed ultrasound (LIPUS) can accelerate tooth movement and preserve tooth and bone integrity during orthodontic treatment. However, the mechanisms by which LIPUS affects tissue remodeling during orthodontic tooth movement (OTM) remain unclear. Periodontal ligament cells (PDLCs) are pivotal in maintaining periodontal tissue equilibrium when subjected to mechanical stimuli. One notable mechano-sensitive ion channel, Piezo1, can modulate cellular function in response to mechanical cues. This study aimed to elucidate the involvement of Piezo1 in the osteogenic response of force-treated PDLCs when stimulated by LIPUS.MethodAfter establishing rat OTM models, LIPUS was used to stimulate rats locally. OTM distance and alveolar bone density were assessed using micro-computed tomography, and histological analyses included hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining and immunohistochemical staining. GsMTx4 and Yoda1 were respectively utilized for Piezo1 functional inhibition and activation experiments in rats. We isolated human PDLCs (hPDLCs) in vitro and evaluated the effects of LIPUS on the osteogenic differentiation of force-treated hPDLCs using real-time quantitative PCR, Western blot, alkaline phosphatase and alizarin red staining. Small interfering RNA and Yoda1 were employed to validate the role of Piezo1 in this process.ResultsLIPUS promoted osteoclast differentiation and accelerated OTM in rats. Furthermore, LIPUS alleviated alveolar bone resorption under pressure and enhanced osteogenesis of force-treated PDLCs both in vivo and in vitro by downregulating Piezo1 expression. Subsequent administration of GsMTx4 in rats and siPIEZO1 transfection in hPDLCs attenuated the inhibitory effect on osteogenic differentiation under pressure, whereas LIPUS efficacy was partially mitigated. Yoda1 treatment inhibited osteogenic differentiation of hPDLCs, resulting in reduced expression of Collagen Ⅰα1 and osteocalcin in the periodontal ligament. However, LIPUS administration was able to counteract these effects.ConclusionThis research unveils that LIPUS promotes the osteogenesis of force-treated PDLCs via downregulating Piezo1.