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The study focuses on an area of relatively mature oil and gas exploration located in the western slope of the Xihu Sag, East China Sea Shelf Basin. Three stratigraphic oil and gas plays are introduced to replenish the shrinking prospect inventory in the area. The reservoirs of these plays are traditional pay intervals of the Eocene Pinghu Formation and Baoshi Formation composed of tide-dominated delta front, tidal flat and delta front sand bar facies. By investigating conventional seismic data, seismic inversion volumes, and well log data, multiple tidal-influenced delta front channels, beach sand packages have been mapped out in different reservoir sand intervals of the Pinghu Formation and Baoshi Formation. We recognize four types of stratigraphic terminations: channel flank pinch-outs, axial pinch-outs of sand-fills, channel mouth sand bar pinch-outs, and onlap pinch-outs for the Baoshi Formation. Both the depositional facies and relatively low sand-shale ratio of the reservoir formations favor the occurrence of stratigraphic terminations. The closure mechanism of all these plays are similar to the traditional structure plays in the area: fault blocks or fault-bounded rollover anticlines, except that one or more closing faults are replaced by these stratigraphic terminations. Several small-sized closures should exist but the relatively large ones are centered around a major intra-slope rise, raising the exploration potential in this maturely explored area. The new exploration drilling campaign has so far tested the play of delta front channel facies, with three out of four wells commercially successful. These play concepts open up a novel approach to identify new traps in the study area and many other rift basins with similar settings in eastern China.

Malignant pleural effusion (MPE) is one of the most common complications of advanced malignant diseases. The patients with MPE have a short survival time and poor prognosis. Clinical therapeutic measures have greatly improved with the deepened exploration of the mechanisms of MPE. Diagnosis hinges on cytology, which is typically based on pleural fluid aspiration or pleural biopsy. Although numerous interventions exist, local palliative treatment is favored for the treatment of MPE. Such treatment aims to alleviate symptoms, such as aggravated dyspnea, and prolong survival time. As molecular targeted therapies and immunotherapies have developed, new diagnostic procedures and treatments have become available for patients with MPE. The recent discovery of the progrowth property of pleural fluid which may be an active promoter of cancer progression suggests that early intervention for the management of MPE may have a positive effect on inhibiting cancer progression and improving prognosis. In coming years, considerable effort should be directed at sophisticated biomarker analysis to select appropriate treatment strategies for the management of MPE.

Abstract This study aimed to evaluate the potential of capping protein (actin filament) muscle Z-line subunit β (CAPZB) messenger ribonucleic acid (mRNA) levels as a biomarker for distinguishing low-grade squamous intraepithelial lesions of the cervix (LSIL) from high-grade squamous intraepithelial lesions of the cervix (HSIL). We collected a total of 166 cervical exfoliated cells and divided them into five groups based on histopathological results. Each sample was divided into two portions, one for fluorescence in situ hybridization (FISH) detection and the other for bisulfite sequencing polymerase chain reaction (BSP) detection. We found that FISH detection of CAPZB mRNA mean fluorescence intensity (MFI) and BSP detection of CAPZB deoxyribonucleic acid (DNA) percentage of methylation rate (PMR) performed as biomarkers for distinguishing HSIL from LSIL, with an area under the receiver operating characteristic curve (AUC), sensitivity, specificity and cut-off value of 0.893, 81.25%, 80.39% and 0.616, 0.794, 64.06%, 81.37% and 0.454, respectively. Furthermore, FISH detection of CAPZB mRNA exhibited a greater AUC (0.893) for the detection of HSIL than the CAPZB DNA methylation method (0.794), indicating the CAPZB mRNA levels can be used as a biomarker for assessing cervical lesions.

Abstract Radiotherapy (RT) is a widely used treatment with strong therapeutic effects, but overcoming challenges related to hypoxia-induced tumor resistance and ineffective antitumor immune responses is crucial for optimal outcomes. In this study, we developed a versatile nanosystem using mesoporous silica nanoparticles (MSNs), R837, and a small quantity of manganese peroxide (Mn/ZnO2). The synthesized MSN@R837-Mn/ZnO2 nanoparticles exhibited precise tumor targeting and accumulation, controlled drug release under acidic conditions, and increased sensitivity in magnetic resonance imaging. These attributes collectively augmented the therapeutic efficacy of RT by alleviating hypoxia and immunosuppression. Tumor cells treated with RT combined with these nanoparticles displayed reduced oxidative stress, alleviated hypoxia, and normalized blood vessel formation. Notably, all mice in the RT + PD-1 + MSN@R837-Mn/ZnO2 group achieved complete tumor regression with extended survival. Safety assessments confirmed the absence of MSN@R837-Mn/ZnO2 toxicity, highlighting its potential as a promising approach with dual functionality for the diagnostic imaging and treatment of cancer.

Abstract Supercapacitor is highly demanded in emerging portable electronics, however, which faces frequent charging and inevitable rapid self-discharging of huge inconvenient. Here, we present a flexible moisture-powered supercapacitor (mp-SC) that capable of spontaneously moisture-enabled self-charging and persistently voltage stabilizing. Based on the synergy effect of moisture-induced ions diffusion of inner polyelectrolyte-based moist-electric generator and charges storage ability of inner graphene electrochemical capacitor, this mp-SC demonstrates the self-charged high areal capacitance of 138.3 mF cm−2 and ~96.6% voltage maintenance for 120 h. In addition, a large-scale flexible device of 72 mp-SC units connected in series achieves a self-charged 60 V voltage in air, efficiently powering various commercial electronics in practical applications. This work will provide insight into the design self-powered and ultra-long term stable supercapacitors and other energy storage devices.

AimThe Triglyceride-Glucose (TyG) index, an indicator of insulin resistance, has been proposed as a predictor of cardiovascular diseases. However, its role in predicting stroke risk, particularly in low-income populations, is not well understood. This study aimed to investigate the predictive value of the TyG index for stroke incidence in a low-income Chinese population, with a focus on gender and age-specific differences.MethodsThis 10-year prospective cohort study included 3,534 participants aged ≥45 years from rural areas in northern China. Baseline data on demographic characteristics, lifestyle factors, and clinical measurements were collected. Participants were followed for stroke incidence, categorized into ischemic and hemorrhagic stroke. Multivariate logistic regression models were used to assess the association between the TyG index and stroke incidence, adjusting for potential confounders.ResultsDuring the follow-up period, 368 participants (10.4%) experienced a stroke, with 327 ischemic and 31 hemorrhagic strokes. TyG index was significantly associated with total and ischemic stroke incidence but not hemorrhagic stroke. After adjusting for confounding factors, for every one standard deviation increase in TyG index, the risk of stroke increased by 32% for overall stroke (RR: 1.32; 95% CI: 1.08-1.61; P=0.006) and 39% for ischemic stroke (RR: 1.39; 95% CI: 1.12-1.73; P=0.003). The risk of stroke in the highest TyG tertile levels (tertile 3) increased by 49% (RR: 1.49; 95% CI 1.11-1.99; P=0.007) for overall stroke, compared to those in the lowest tertile levels (tertile 1). For ischemic stroke, the risk of stroke increased by 53% (RR: 1.53; 95% CI 1.12-2.11; P=0.008) in the highest TyG tertile levels (tertile 3) compared to those in the lowest tertile levels (tertile 1).ConclusionThis 10-year prospective cohort study has established the TyG index as an independent predictor of both total and ischemic stroke incidence in a low-income Chinese population. The findings indicate that the TyG index is particularly effective in predicting stroke risk among women and older adults (≥60 years), but not for hemorrhagic stroke. These insights are crucial for improving clinical practice and stroke prevention strategies.

Maize is one of the most successful crops in utilizing heterosis which significantly improves maize stresses resistance and yield. Drought is a destructive abiotic stress that significantly reduces crop yield, particularly in maize. Drought stress and re-watering frequently occur during the growth and development of maize; however, the molecular mechanisms of heterosis under drought stress and re-watering have rarely been systematically investigated. Zhengdan7137 and Zhengdan7153 are two maize hybrid varieties with robust heterosis, and separately belongs to the SS×NSS and Reid×Tangsipingtou heterotic groups. 54 transcriptomes of these two hybrids and their parental inbred lines were analyzed under well-watering (WW), water-deficit (WD), and re-watering (RW) conditions using RNA-Seq. In this study, we identified 3,411 conserved drought response genes (CDRGs) and 3,133 conserved re-watering response genes (CRRGs) between Zhengdan7137 and Zhengdan7153. When comparing CDRGs and CRRGs to overdominance and underdominance genes, we identified 303 and 252 conservative drought response overdominance genes (DODGs) and underdominance genes (DUDGs), respectively, and 165 and 267 conservative re-watering response overdominance genes (RODGs) and underdominance genes (RUDGs), respectively. DODGs are involved in stress response-related processes, such as L-phenylalanine metabolism, carbohydrate metabolism, and heat response, whereas DUDGs are associated with glucose metabolism, pentose-phosphate shunt, and starch metabolism. RODGs and RUDGs contribute to the recovery of hybrids from drought stress by upregulating cell propagation and photosynthesis processes, and repressing stress response processes, respectively. It indicated overdominant and underdominant genes conservatively contributed to hybrid heterosis under drought stress. These results deepen our understanding of the molecular mechanisms of drought resistance, uncover conservative molecular mechanisms of heterosis under drought stress and re-watering, and provide potential targets for improving drought resistance in maize.

Hevea brasiliensis is an important cash crop with the product named natural rubber (NR) for markets. Ethylene (ET) is the most effective yield stimulant in NR production but the molecular mechanism remains incomplete. Here, latex properties analysis, transcriptome analysis, and metabolic profiling were performed to investigate the mechanism of NR yield increase in four consecutive tappings after ET stimulation. The results revealed that sucrose and inorganic phosphate content correlated positively with dry-rubber yield and were induced upon ET stimulation. Stimulation with ET also led to significant changes in gene expression and metabolite content. Genes involved in phytohormone biosynthesis and general signal transduction as well as 51 transcription factors potentially involved in the ET response were also identified. Additionally, KEGG annotation of differentially accumulated metabolites suggested that metabolites involved in secondary metabolites, amino-acid biosynthesis, ABC transporters, and galactose metabolism were accumulated in response to ET. Integrative analysis of the data collected by transcriptomics and metabolomics identified those differentially expressed genes and differentially accumulated metabolites are mainly involved in amino-acid biosynthesis and carbohydrate metabolism. Correlation analysis of genes and metabolites showed a strong correlation between amino-acid biosynthesis during ET stimulation. These findings provide new insights into the molecular mechanism underlying the ET-induced increase in rubber yield and further our understanding of the regulatory mechanism of ethylene signaling in rubber biosynthesis.

Abstract Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.

Heavy rainfall is the main factor triggering geological disasters. In the northern region of China, most of the researches focus on the geologic disasters caused by short-term heavy rainfall, and the researches on the characteristics of geologic disasters under regional extreme precipitation conditions are still insufficient. Based on the sample analysis of geological disasters triggered by the “23•7” heavy rainfall, the regular characteristics of geological disasters in the Hebei section of the Taihang Mountains were studied. The results show that: (1) geologic hazards show the trend of multiple and group occurrence, and the number of occurrences reaches a new high in history, and the types of avalanches, landslides, and mudslides are the main ones, which stimulate new geologic hazards to increase significantly; (2) the spatial and temporal scales of occurrence of geologic hazards and the area of heavy rainfall are highly coincident with each other, and the south and north sections of the Taihang Mountains show a differentiated distribution; (3) mudslides cause the most damage, and slope-type mudslides are obviously more frequent, and the loose material-covered landslides are more frequent and easier to occur. cover type landslides are more frequent and prone to occur. The results of the study can provide a reference for the prevention of geologic disasters under extreme precipitation conditions.

ObjectiveTo evaluate the antitumor effects of diisopropylamine dichloroacetate (DADA) alone or in combination with chemotherapy/radiotherapy/immunotherapy in NSCLC and explore the underlying mechanisms involved.MethodsMTT, UV spectrophotometry, flow cytometry, fluorescence microscopy, and clonogenic survival assays were used. In LLC mouse models, the antitumor effects of radiotherapy, DADA, and the anti-PD-1 antibody alone or in combination were evaluated, and the T cell numbers were evaluated in different groups.ResultsDADA significantly inhibited lactate production and promoted apoptosis in NSCLC in vitro. Compared with pemetrexed or DADA alone, the combination of DADA with pemetrexed significantly inhibited proliferation and promoted apoptosis (p

Background: The real-world clinical impact of mNGS on BALF in the respiratory intensive care unit (RICU) is not yet fully understood. Methods: We investigated the clinical impact of mNGS on BALF samples obtained from 92 patients admitted to the RICU over a 2-year period. We utilized both mNGS and culture methods to evaluate the effectiveness of mNGS in diagnosing pulmonary infections. The clinical impact of mNGS were evaluated by the clinician committees. Results: Among the 92 diagnosed patients, 78 cases (84.7 %) were determined to have infectious diseases caused by pathogenic microorganisms, and the bacterial infections constituted the most prevalent diagnostic category. For mixed infection, the most common type was the Pneumocystis jironecii and cytomegalovirus co-infection. The mNGS results had a positive impact on the clinical management of 43 cases (46.7 %). Moreover, 19 cases (44.2 %) of positive clinical impacts were solely based on new diagnoses made possible by mNGS results. These new diagnoses were particularly helpful for identifying rare pathogens, which could not be detected by conventional diagnostic methods. Conclusions: The BALF mNGS has a positive real-world impact in RICU. Clinician committee play a critical role in ensuring the appropriate use of mNGS.

Background: Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. Methods: An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. Results: This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95 % Confidence Interval (CI) -2.98 to 8.44; p > 0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26 %, 95 % CI 7.24 to 51.28; p = 0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95 % CI -2.36 to 7.06; p = 0.33]. Conclusion: The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. PROSPERO: 2023 CRD42023493930

Obesity, characterized by its complexity and heterogeneity, has emerged as a significant public health concern. Its association with increased incidence and mortality of cardiovascular diseases stems not only from its complications and comorbidities but also from the endocrine effects of adipose tissue. Abdominal aortic aneurysm (AAA), a chronic inflammatory condition, has been closely linked to obesity. Intriguingly, mild obesity appears to confer a protective effect against AAA mortality, whereas severe obesity and being underweight do not, giving rise to the concept of the “obesity paradox”. This review aims to provide an overview of obesity and its paradoxical relationship with AAA, elucidate its underlying mechanisms, and discuss the importance of preoperative weight loss in severely obese patients with AAA.

BackgroundThe Stenotrophomonas maltophilia complex (Smc) has emerged as a significant nosocomial pathogen contributing to increased mortality rates, particularly in case of bloodstream infections.MethodsThis study employed whole-genome sequencing (WGS) to assess the genetic diversity, antimicrobial resistance profiles, molecular epidemiology and frequencies of virulence genes among 55 S. maltophilia isolates obtained from bacteremic cases over a 9-year period.ResultsBased on the threshold of 95% average nucleotide identity (ANI) and 70% digital DNA–DNA hybridization (dDDH) for genospecies delineation, we classified 37 isolates into 6 known species, all belonging to the Smc. The remaining 18 isolates sequenced in this study were assigned to 6 new genomospecies. Among the 55 isolates, we identified 44 different sequence types (STs), comprising 22 known and 22 novel allele combinations. The resistance rate of Smc against trimethoprim-sulfamethoxazole (TMP/SMX) was found to be 3.6%, with the sul1 and class one integron integrase genes (intI) detected in these isolates. All Smc isolates were susceptible to minocycline. Furthermore, all Smc strains harbored the motA, pilU, smf-1 and Stmpr2 genes. Genomospecies 1 (100%, n = 9), Stenotrophomonas maltophilia (84.21%, n = 19) and Stenotrophomonas sepilia (71.43%, n = 7) demonstrated a higher percentage of the afaD gene, which was also associated with a higher separation rate. In addition to motA, pilU, smf-1, and Stmpr2 genes, all S. maltophilia strains (100%) contained entA, gspD, KatA, and stmPr1 genes, while all genomospecies 1 strains (100%) contained afaD, entA, gspD, and KatA genes.ConclusionOur study highlights the genetic diversity among Smc isolates from patients with bacteremia, revealing 22 novel ST types, 58 new alleles and 6 new genomospecies. S. maltophilia and S. pavanii were found to carry more virulence factors, emphasizing the importance of accurate strain identification. Minocycline emerged as a promising alternative antibiotic for patients who were resistant to TMP/SMX.

ABSTRACT Accurate species-level identification of Enterobacter cloacae complex (ECC) is crucial for related research. The classification of ECC is based on strain-to-strain phylogenetic congruence, as well as genomic features including average nucleotide identity (ANI) and digitalized DNA-DNA hybridization (dDDH). ANI and dDDH derived from whole-genome sequencing have emerged as a reliable metric for assessing genetic relatedness between genomes and are increasingly recognized as a standard for species delimitation. Up to now, there are two different classification methods for ECC. The first one categorizes E. hormaechei, a species within ECC, into five subspecies (E. hormaechei subsp. steigerwaltii, subsp. oharae, subsp. xiangfangensis, subsp. hoffmannii, and subsp. hormaechei). The second classifies E. hormaechei as three species: E. hormaechei, “E. xiangfangensis,” “E. hoffmanii.” While the former is well-accepted in the academic area, the latter may have a greater ability to distinguish different species of ECC. To assess the suitability of these identification criteria for clinical ECC isolates, we conducted a comprehensive analysis involving phylogenetic analysis, ANI and dDDH value alignment, virulence gene identification, and capsule typing on 256 clinical ECC strains isolated from the bloodstream. Our findings indicated that the method of categorizing E. hormaechei into five subspecies has better correlation and consistency with the molecular characteristics of clinical ECC isolates, as evidenced by phylogenetic analysis, virulence genes, and capsule typing. Therefore, the subspecies-based classification method appears more suitable for taxonomic assignments of clinical ECC isolates.IMPORTANCEStandardizing taxonomy of the Enterobacter cloacae complex (ECC) is necessary for data integration across diverse studies. The study utilized whole-genome data to accurately identify 256 clinical ECC isolated from bloodstream infections using average nucleotide identity (ANI), digitalized DNA-DNA hybridization (dDDH), and phylogenetic analysis. Through comprehensive assessments including phylogenetic analysis, ANI and dDDH comparisons, virulence gene, and capsule typing of the 256 clinical isolates, it was concluded that the classification method based on subspecies exhibited better correlation and consistency with the molecular characteristics of clinical ECC isolates. In summary, this research contributes to the precise identification of clinical ECC at the species level and expands our understanding of ECC.

Abstract Background Attention provides the foundation for cognitions, which was shown to be affected by microwave (MW) radiation. With the ubiquitous of microwaves, public concerns regarding the impact of MW radiation on attention has hence been increased. Our study aims to investigate the potential effect and mechanism of acute microwave exposure on attention. Results We identified obvious impairment of attention in mice by the five-choice serial reaction time (5-CSRT) task. Proteomic analysis of the cerebrospinal fluid (CSF) revealed neuroinflammation and microglial activation potentially due to acute MW exposure. Moreover, biochemical analysis further confirmed microglial activation in the prefrontal cortex (PFC) of mice subjected to acute MW exposure. Finally, minocycline, a commercially available anti-inflammatory compound, attenuated neuroinflammation, inhibited the upregulation of N-methyl-D-aspartic acid receptor (NMDAR) including NR2A and NR2B, and also accelerated the attentional recovery after MW exposure. Conclusions We believe that microglial activation and NMDAR upregulation likely contribute to inattention induced by acute MW exposure, and we found that minocycline may be effective in preventing such process.

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity. In practical application, the research of food combinations is more significant than a specific food component. This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid (OA). Five indexes, triglyceride (TG), total cholesterol (T-CHO), low density lipoprotein-cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), were used to evaluate the lipid-lowering effect of highland barley extract. We also preliminary studied the lipid-lowering mechanism by Real-time fluorescent quantitative polymerase chain reaction (qPCR). The results indicated that highland barley extract contains many components with lipid-lowering effects, such as hyperoside and scoparone. In vitro, the lipase assay showed an 18.4 % lipase inhibition rate when the additive contents of highland barley extract were 100 µg/mL. The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mM OA-induced HepG2 cells. The results showed that intracellular TG, LDL-C, and T-CHO content decreased by 34.4 %, 51.2 %, and 18.4 %, respectively. ALT and AST decreased by 51.6 % and 20.7 % compared with the untreated hyperlipidemic HepG2 cells. qPCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγ and Fabp4.

Lung cancer is the leading cause of cancer-related deaths worldwide. Bone is a common metastatic site of lung cancer, about 50% of bone metastatic patients will experience skeletal related events (SREs). SREs not only seriously impact the quality of life of patients, but also shorten their survival time. The treatment of bone metastasis requires multi-disciplinary therapy (MDT) and development of individualized treatment plan. In order to standardize the diagnosis and treatment of bone metastasis in lung cancer, the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.

Abstract The breakthrough of programmed cell death protein 1 (PD‐1) blockade therapy has changed the clinical treatment of non‐small cell lung cancer (NSCLC) in the past few years. The success of PD‐1 blockade therapy has been attributed to high tumor mutation burden and high immunogenicity of lung cancer cells. To further improve the efficacy of NSCLC immunotherapy and overcome the resistance of lung cancer cells to immune checkpoint blockade, new approaches that enhance the active immune response, such as neoantigen vaccines and cellular‐based therapies, are urgently required. Neoantigens are considered ideal targets for cancer immunotherapy because of their high immunogenicity and specificity. In this mini review, we first discuss the current advances in neoantigen vaccines for treating cancers and then review the results of preclinical studies and early‐phase human clinical trials of neoantigen‐based therapies for NSCLC. Finally, we focus on the identification of neoantigens in patients with NSCLC and review the candidate mutations reported by recent studies and our investigations. The review concludes that, in addition to immune checkpoint blockade, approaches targeting neoantigens are promising for improving the efficacy of NSCLC immunotherapy.

Background and objective The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. Methods We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. Results All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. Conclusion Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

Abstract Background Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates β-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. Method Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). “Hegu” (LI4), “Neiguan” (PC6) and “Zusanli” points (ST36) were selected, and a “HANS” percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum β-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100β, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). Results The dosage of remifentanil in the T group was reduced compared to that in the S group (P

When two resonators of coupled silicon resonators are identical and the gain on one side is equal to the loss on the other side, a parity-time (PT) symmetric-coupled silicon resonator is formed. As non-Hermitian systems, the PT-symmetric systems have exhibited many special properties and interesting phenomena. This paper proposes the strain-induced frequency splitting in PT symmetry-coupled silicon resonators. The frequency splitting of the PT system caused by strain perturbations is derived and simulated. Theory and simulation both indicate that the PT system is more sensitive to strain perturbation near the exceptional point (EP) point. Then, a feedback circuit is designed to achieve the negative damping required for PT symmetry. Based on a simple silicon-on-insulator (SOI) process, the silicon resonator chip is successfully fabricated. After that, the PT-symmetric-coupled silicon resonators are successfully constructed, and the frequency splitting phenomenon caused by strain is observed experimentally.

In order to investigate the relationship between the molecular structure of fibers and the differences in physicochemical interactions between fibers and asphalt on the performance of fiber-modified asphalt, this paper chose two types of fibers with different chemical structures: straw fiber and polyester fiber. First, the differences in molecular interactions between the two fibers and asphalt were explored using molecular dynamics, then the differences in the adsorption capacity of the two fibers on asphalt components were tested by attenuated total reflection infrared spectroscopy experiments, and finally, the differences in the rheological properties of the two fiber-modified asphalts were tested by dynamic shear rheology and low-temperature creep experiments. The molecular dynamics simulation findings reveal that polyester fibers may intersperse into asphalt molecules and interact with them via structures such as aromatic rings, whereas straw fibers are merely adsorbed on the asphalt’s surface. Straw fibers and asphalt exhibit hydrogen bonding, whereas polyester fibers and asphalt display van der Waals interactions. The results of attenuated total reflectance infrared spectroscopy indicated that polyester fiber absorbed asphalt components better than straw fiber. The rheological tests revealed that the polyester fiber had the highest complex shear modulus in the temperature range of 46–82 °C, and at 64 °C, the phase angle was 4.289° lower than that of the straw fiber-treated bitumen. Polyester fiber-modified asphalt had a 32.48%, 15.72%, and 6.09% lower creep modulus than straw fiber-modified asphalt at three low-temperature conditions: −6 °C, −12 °C, and −18 °C. It is clear that fibers with aromatic rings as a chemical structure outperform lignin-based fibers in terms of improving asphalt characteristics. The research findings can serve as a theoretical foundation for the selection of fibers to produce fiber-modified asphalt.

S-metolachlor is a selective pre-emergence herbicide used in dryland. However, it is challenging to employ in paddy fields due to its phytotoxic effects on rice. As a common phytohormone, Gibberellin-3 (GA3) is inferred to have the ability to alleviate herbicide phytotoxicity. This study first quantitatively verified the phytotoxicity of s-metolachlor to rice and then demonstrated the mitigative effect of GA3 on these adverse reactions. Furthermore, a transcriptome of rice seedlings subjected to different treatments was constructed to assemble the reference genes, followed by comparative metabolomics and proteomics analyses. Metabolomics revealed an enrichment of flavonoid metabolites in the group of adding GA3, and these flavonoids can eliminate ROS in plants. Proteomics analysis indicated that differential proteins were enriched in the phenylpropanoid biosynthesis pathway responsible for the synthesis of flavonoids and that the functions of most differential proteins are associated with peroxidase. The proteome, combined with the transcriptome, revealed that the expressions of proteins and genes was related to the POD activity in the group of adding GA3. It was speculated that the elimination of ROS is key to alleviating the stress of s-metolachlor on rice growth. It was inferred that the mechanism of GA3 in alleviating the phytotoxicity of the substance s-metolachlor is by increasing the activity of the POD and influencing the growth of rice seedlings through the restoration of flavonoid synthesis. In this study, we screened GA3 as a safener to alleviate the phytotoxicity of s-metolachlor on rice. On this basis, the mechanism of alleviating phytotoxicity was studied. The application range of s-metolachlor might be expanded, providing a new supplementary method for weed control and herbicide resistance management.

BackgroundPerivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.MethodsSprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.ResultsChronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.ConclusionRegular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.

Black phosphorus nanotubes (BPNTs) may have good properties and potential applications. Determining the vibration property of BPNTs is essential for gaining insight into the mechanical behaviour of BPNTs and designing optimized nanodevices. In this paper, the mechanical behaviour and vibration property of BPNTs are studied via orthotropic cylindrical shell model and molecular dynamics (MD) simulation. The vibration frequencies of two chiral BPNTs are analysed systematically. According to the results of MD calculations, it is revealed that the natural frequencies of two BPNTs with approximately equal sizes are unequal at each order, and that the natural frequencies of armchair BPNTs are higher than those of zigzag BPNTs. In addition, an armchair BPNTs with a stable structure is considered as the object of research, and the vibration frequencies of BPNTs of different sizes are analysed. When comparing the MD results, it is found that both the isotropic cylindrical shell model and orthotropic cylindrical shell model can better predict the thermal vibration of the lower order modes of the longer BPNTs better. However, for the vibration of shorter and thinner BPNTs, the prediction of the orthotropic cylindrical shell model is obviously superior to the isotropic shell model, thereby further proving the validity of the shell model that considers orthotropic for BPNTs.

Abstract Colloidal semiconductor nanoplatelets (NPLs) have emerged as low‐cost and free‐standing alternates of traditional quantum wells. The giant heavy‐ and light‐hole splitting in NPLs allows for efficient optical spin injection. However, the electron spin lifetimes for prototypical CdSe NPLs are within a few picoseconds, likely limited by strong electron‐hole exchange in these quantum‐ and dielectric‐confined materials. Here how this hurdle can be overcome with engineered NPL‐heterostructures is demonstrated. By constructing type‐I CdSe/ZnS core/shell NPLs, dielectric screening inside the core is strongly enhanced, prolonging the electron spin polarization time (τesp) to over 30 ps (or 60 ps electron spin‐flip time). Alternatively, by growing type‐II CdSe/CdTe core/crown NPLs to spatially separate electron and hole wavefunctions, the electron‐hole exchange is strongly suppressed, resulting in τesp as long as 300 ps at room temperature. This study not only exemplifies how the well‐established synthetic chemistry of colloidal heterostructures can aid in spin dynamics control but also establishes the feasibility of room‐temperature coherent spin manipulation in colloidal NPLs.

Background and objective In recent years, immunotherapy represented by programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunosuppressants has greatly changed the status of non-small cell lung cancer (NSCLC) treatment. PD-L1 has become an important biomarker for screening NSCLC immunotherapy beneficiaries, but how to easily and accurately detect whether PD-L1 is expressed in NSCLC patients is a difficult problem for clinicians. The aim of this study was to construct a Nomogram prediction model of PD-L1 expression in NSCLC patients based on 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography/conputed tomography (PET/CT) metabolic parameters and to evaluate its predictive value. Methods Retrospective collection of 18F-FDG PET/CT metabolic parameters, clinicopathological information and PD-L1 test results of 155 NSCLC patients from Inner Mongolia People's Hospital between September 2016 and July 2021. The patients were divided into the training group (n=117) and the internal validation group (n=38), and another 51 cases of NSCLC patients in our hospital between August 2021 and July 2022 were collected as the external validation group according to the same criteria. Then all of them were categorized according to the results of PD-L1 assay into PD-L1+ group and PD-L1- group. The metabolic parameters and clinicopathological information of patients in the training group were analyzed by univariate and binary Logistic regression, and a Nomogram prediction model was constructed based on the screened independent influencing factors. The effect of the model was evaluated by receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) in both the training group and the internal and external validation groups. Results Binary Logistic regression analysis showed that metabolic tumor volume (MTV), gender and tumor diameter were independent influences on PD-L1 expression. Then a Nomogram prediction model was constructed based on the above independent influences. The ROC curve for the model in the training group shows an area under the curve (AUC) of 0.769 (95%CI: 0.683-0.856) with an optimal cutoff value of 0.538. The AUC was 0.775 (95%CI: 0.614-0.936) in the internal validation group and 0.752 (95%CI: 0.612-0.893) in the external validation group. The calibration curves were tested by the Hosmer-Lemeshow test and showed that the training group (χ2=0.040, P=0.979), the internal validation group (χ2=2.605, P=0.271), and the external validation group (χ2=0.396, P=0.820) were well calibrated. The DCA curves show that the model provides clinical benefit to patients over a wide range of thresholds (training group: 0.00-0.72, internal validation group: 0.00-0.87, external validation group: 0.00-0.66). Conclusion The Nomogram prediction model constructed on the basis of 18F-FDG PET/CT metabolic parameters has greater application value in predicting PD-L1 expression in NSCLC patients.

Abstract Complex metal nanoparticles distributed uniformly on supports demonstrate distinctive physicochemical properties and thus attract a wide attention for applications. The commonly used wet chemistry methods display limitations to achieve the nanoparticle structure design and uniform dispersion simultaneously. Solid-phase synthesis serves as an interesting strategy which can achieve the fabrication of complex metal nanoparticles on supports. Herein, the solid-phase synthesis strategy is developed to precisely synthesize uniformly distributed CoFe@FeOx core@shell nanoparticles. Fe atoms are preferentially exsolved from CoFe alloy bulk to the surface and then be carburized into a FexC shell under thermal syngas atmosphere, subsequently the formed FexC shell is passivated by air, obtaining CoFe@FeOx with a CoFe alloy core and a FeOx shell. This strategy is universal for the synthesis of MFe@FeOx (M = Co, Ni, Mn). The CoFe@FeOx exhibits bifunctional effect on regulating polysulfides as the separator coating layer for Li-S and Na-S batteries. This method could be developed into solid-phase synthetic systems to construct well distributed complex metal nanoparticles.

Abstract In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43–50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6–4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8–4.0 and 3.5–3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.

Due to its excellent electrical performance, mechanical reliability, and thermal stability, electroplated gold is still the most commonly used material for movable beams in RF MEMS switches. This paper investigates the influence of process conditions on the quality and growth rate of gold electroplating, and the optimized process parameters for the gold electroplating process are obtained. The characterization of the optimized electroplated gold layer shows that it has small surface roughness and excellent thermal stability. With this optimized gold electroplating process, the RF MEMS switches are fabricated and hermetic packaged. In order to obtain the temperature environment adaptability of the packaged switch, the influence of working temperature is studied. The temperature effects on mechanical performance (includes pull-in voltage and lifetime) and RF performance (includes insertion loss and isolation) are revealed.

In response to the fracturing disturbance problem in the Mahu 18 block, based on the production data of on-site fracturing disturbance well groups, the actual fracturing disturbance cases in the block were first statistically divided. The complex fracturing disturbance situation in the block was divided according to the relationship between the number of fracturing wells and the number of production wells. Then, the disturbance types were classified based on the production dynamic response characteristics of the disturbed wells, and the degree of disturbance was quantitatively evaluated for the different types. The results indicate two main types of fracturing interference in the Mahu 18 block: the fracture communication type, and the pressure wave interference type formed through inter-well connectivity through the reservoir matrix. The fracturing disturbance dominated by fracture communication can cause serious water channeling to the production well through the direct connection of inter-well fractures, leading to a surge in water production. This type of fracturing disturbance often has a severe negative impact on the production well. In addition, the pressure and production (water production, liquid production, oil production) in the production dynamic response characteristics of disturbed wells during fracturing disturbance were used as evaluation indicators to quantify the impact of different types of fracturing disturbance from multiple perspectives.

Macadamia nuts are one of the most important economic food items in the world. Pericarp thickness and flavonoid composition are the key quality traits of Macadamia nuts, but the underlying mechanism of pericarp formation is still unknown. In this study, three varieties with significantly different pericarp thicknesses, namely, A38, Guire No.1, and HAES 900, at the same stage of maturity, were used for transcriptome analysis, and the results showed that there were significant differences in their gene expression profile. A total of 3837 new genes were discovered, of which 1532 were functionally annotated. The GO, COG, and KEGG analysis showed that the main categories in which there were significant differences were flavonoid biosynthesis, phenylpropanoid biosynthesis, and the cutin, suberine, and wax biosynthesis pathways. Furthermore, 63 MiMYB transcription factors were identified, and 56 R2R3-MYB transcription factors were clustered into different subgroups compared with those in Arabidopsis R2R3-MYB. Among them, the S4, S6, and S7 subgroups were involved in flavonoid biosynthesis and pericarp formation. A total of 14 MiMYBs’ gene expression were verified by RT-qPCR analysis. These results provide fundamental knowledge of the pericarp formation regulatory mechanism in macadamia nuts.

Tau protein is a microtubule-associated protein that is widely distributed in the central nervous system and maintains and regulates neuronal morphology and function. Tau protein aggregates abnormally and forms neurofibrillary tangles in neurodegenerative diseases, disrupting the structure and function of neurons and leading to neuronal death, which triggers the initiation and progression of neurological disorders. The aggregation of tau protein in neurodegenerative diseases is associated with post-translational modifications, which may affect the hydrophilicity, spatial conformation, and stability of tau protein, promoting tau protein aggregation and the formation of neurofibrillary tangles. Therefore, studying the role of tau protein in neurodegenerative diseases and the mechanism of aberrant aggregation is important for understanding the mechanism of neurodegenerative diseases and finding therapeutic approaches. This review describes the possible mechanisms by which tau protein promotes neurodegenerative diseases, the post-translational modifications of tau protein and associated influencing factors, and the current status of drug discovery and development related to tau protein, which may contribute to the development of new therapeutic approaches to alleviate or treat neurodegenerative diseases.

Macadamia nut plantings in China are expanding year by year. In order to breed and promote superior varieties, this study analyzed the effects of different rootstocks and scions on the survival rate of grafted seedlings, and then selected the best substrate composition for plant growth. The results showed that the survival rate of the HAES788 variety as rootstock and Guire No. 1 as scion was the highest, reaching 96%. The optimal grafting time in December was better than that in March. Furthermore, among 16 substrate formulations, T12, T13, T15, and T16 had advantages of agglomerated soil and more well-developed root systems compared to the CK made of loess. The plant height, stem diameter, leaf length, leaf width, and dry weight of the aboveground and underground parts of the grafted seedlings planted in these substrate formulations were significantly higher than those plants planted in the CK. In addition, the substrate formulations T12, T13, T15, and T16 significantly improved the organic matter, total nitrogen, and total potassium content of the substrate soils, but little improvement was observed for total phosphorus content after 13 months. Overall, macadamia grafting times are best in December, with HAES788 and Guire No. 1 being the best rootstock and scion. The optimal substrate formulations are T12, T13, T15, and T16. This study provides a solid foundation for the production of high-quality macadamia plants.

Abstract Single layer diamond—diamane, has been reported with excellent mechanical properties. In this work, molecular dynamics (MD) simulation and Kirchhoff plate model are utilized to investigate the vibrational characteristics of diamane sheets. The mechanical parameters of diamane sheets, including bending stiffness, Young’s modulus, Poisson’s ratio and coefficient of thermal expansion, are calibrated by using MD simulations. The natural frequencies and corresponding modal shapes of the diamane sheets predicted by the Kirchhoff plate model agree well with that obtained from the MD simulations. It is found that the edges exert marginal effect on the modal shapes when free boundary conditions are applied. Additionally, the Kirchhoff plate model considering the thermal expansion provides reasonable prediction for the natural frequencies of the diamane sheets with all boundary clamped under varying temperatures. This study offers valuable insights into the vibrational properties of diamane sheets, from both a simulation and theoretical standpoint. The findings would be beneficial for the design of nanoscale mechanical resonators utilizing these novel carbon materials.

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly used in the management of type 2 diabetes mellitus (T2DM) and have been found to worsen the reduction of skeletal muscle mass in individuals with T2DM. This study aims to examine the potential of exercise in mitigating the skeletal muscle atrophy induced by SGLT2i treatment. Methods A rat model of T2DM (40 male Sprague-Dawley rats; T2DM induced by a combination of high-fat diet and streptozotocin) was used to examine the effects of six-week treatment with Dapagliflozin (DAPA, SGLT2i) in combination with either aerobic exercise (AE) or resistance training (RT) on skeletal muscle. T2DM-eligible rats were randomized into the T2DM control group (CON, n = 6), DAPA treatment group (DAPA, n = 6), DAPA combined with aerobic exercise intervention group (DAPA + AE, n = 6), and DAPA combined with resistance training intervention group (DAPA + RT, n = 6). To assess the morphological changes in skeletal muscle, myosin ATPase and HE staining were performed. mRNA expression levels of Atrogin-1, MuRF1, and Myostatin were determined using quantitative PCR. Furthermore, protein expression levels of AKT, p70S6K, mTOR, FoXO1/3A, NF-κB, and MuRF1 were examined through western blotting. Results Both the administration of DAPA alone and the combined exercise intervention with DAPA resulted in significant reductions in blood glucose levels and body weight in rats. However, DAPA alone administration led to a decrease in skeletal muscle mass, whereas RT significantly increased skeletal muscle mass and muscle fiber cross-sectional area. The DAPA + RT group exhibited notable increases in both total protein levels and phosphorylation levels of AKT and p70S6K in skeletal muscle. Moreover, the DAPA, DAPA + AE, and DAPA + RT groups demonstrated downregulation of protein expression (FoXO1/3A) and mRNA levels (Atrogin-1, MuRF1, and Myostatin) associated with muscle atrophy. Conclusions Our findings provide support for the notion that dapagliflozin may induce skeletal muscle atrophy through mechanisms unrelated to protein metabolism impairment in skeletal muscle, as it does not hinder protein metabolic pathways while reduces muscle atrophy-related genes. Additionally, our observations reveal that RT proves more effective than AE in enhancing skeletal muscle mass and muscle fiber cross-sectional area in rats with T2DM by stimulating protein anabolism within the skeletal muscle.

This paper focuses on the cooperative driving challenges of connected and automated vehicles (CAVs) at single-lane roundabouts. First, a geometric path planning method is proposed for CAVs navigating a single-lane roundabout. Based on this method, a vehicle roundabout model is established. Four potential traffic scenarios for CAVs are established, and the optimal arrival times at conflict points are analyzed. By correlating the optimal arrival times at conflict points with the optimal entry times into the roundabout, the multi-vehicle coordination problem in complex intersections is simplified to a speed control issue during entry. Utilizing the principles of optimal control and Pontryagin minimization, two speed optimization strategies are proposed. Finally, MATLAB is employed for simulation analysis. The results indicate that the control strategy proposed in this paper enables the system to clearly identify potential conflicts between vehicles and implement an optimal control strategy, ensuring that vehicles can navigate the roundabout efficiently in terms of time and fuel without collisions. Additionally, the minimum time interval is established at 0.2 seconds to completely prevent vehicle collisions. In this study, the fusion problem involving two vehicles at a single conflict point is further expanded to encompass multiple vehicles at multiple conflict points. Thus, the efficient scheduling of multiple vehicles in single-lane roundabouts is realized.

Metastatic carcinoma of the paranasal sinuses in lung cancer is an extremely uncommon condition. We report here a 57-year-old female patient with epidermal growth factor receptor (EGFR)-positive stage IV non-small cell lung cancer (NSCLC) with multiple bone metastases. After resistance to second- and third-generation EGFR-tyrosine kinase inhibitors (TKIs), the patient presented with headache accompanied by progressively enlarging lesions of the nasal cavity on CT scan. Further endoscopic sinus neoplasmectomy confirmed sinus metastasis of lung adenocarcinoma. Although subsequent chemotherapy and immunotherapy were both administered, the disease continued to progress, and the patient passed away 21 months after diagnosis. Combined with real-time dynamic next-generation sequencing (NGS) during the different generations of EGFR-TKI treatments and dynamic tumour microenvironment analysis, we discussed the clinical manifestations of sinus metastasis and the molecular biology and tumour immune microenvironment changes after resistance to the second-and third- generation of EGFR-TKI therapy.

Developing solar‐driven desalination through interfacial steam generation is crucial to reducing global water shortages. However, traditional solar steam generation systems have faced efficiency, durability, cost, and complexity limitations. To overcome these issues, interfacial solar steam evaporators are fabricated using light‐absorbing materials with low thermal conductivity, high absorption capacity, and sufficient mechanical strength. Herein, an advanced 3D solar evaporator is developed by coating MXene onto the surface of the aramid nanofiber aerogels (MX@ANF aerogels). The MXene coating enhances the ANF aerogels' light absorption and thermal conversion capabilities. Additionally, the hydrophilicity of MXene complements the high porosity of the host aerogels, enhancing continuous water supply by improving the capillary action. Primarily, these MX@ANF aerogels show promising performance at the air–water interface, with an evaporation rate of 1.48 kg m−2 h−1 and steam conversion efficiency of 93.8% under 1 sun irradiation (1 kW m−2). These highlight the effectiveness of the MX@ANF aerogel as a material for solar‐driven desalination. Moreover, using MXene as a photothermal agent in composite materials paves new avenues toward efficient and cost‐effective solutions for addressing water scarcity through solar desalination.

Summary: Background: Essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), has a substantial risk of evolving into post-essential thrombocythemia myelofibrosis (post-ET MF). This study aims to establish a prediction nomogram for early prediction of post-ET MF in ET patients. Methods: The training cohort comprised 558 patients from 8 haematology centres between January 1, 2010, and May 1, 2023, while the external validation cohort consisted of 165 patients from 6 additional haematology centres between January 1, 2010, and May 1, 2023. Univariable and multivariable Cox regression analysis was performed to identified independent risk factors and establish a nomogram to predict the post-ET MF free survival. Both bias-corrected area under the curve (AUC), calibration curves and concordance index (C-index) were employed to assess the predictive accuracy of the nomogram. Findings: Multivariate Cox regression demonstrated that elevated red blood cell distribution width (RDW), elevated levels of lactate dehydrogenase (LDH) and the level of haemoglobin (Hb), a history of smoking and the presence of splenomegaly were independent risk factors for post-ET MF. The C-index displayed of the training and validation cohorts were 0.877 and 0.853. The 5 years, 10 years AUC values in training and external validation cohorts were 0.948, 0.769 and 0.978, 0.804 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction. Interpretation: We developed a nomogram capable of predicting the post-ET MF free survival probability at 5 years and 10 years in ET patients. This tool helps doctors identify patients who need close monitoring and appropriate counselling. Funding: This research was funded by the Key R&D Program of Zhejiang (No. 2022C03137); the Public Technology Application Research Program of Zhejiang, China (No. LGF21H080003); and the Zhejiang Medical Association Clinical Medical Research special fund project (No. 2022ZYC-D09).

Type 2 diabetes mellitus (T2DM) is a prevalent, chronic metabolic disease. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and aerobic exercise (AE) have shown promise in mitigating insulin resistance (IR) and T2DM. This study investigated the effects of dapagliflozin (Dapa) monotherapy and combined AE on mitochondrial quality control (MQC) in skeletal muscle and IR in T2DM rats. T2DM rats, induced by a high-fat diet/streptozotocin model, were randomly assigned to the following groups: T2DM+vehicle group (DMV), T2DM rats treated with Dapa (DMDa, 10 mg/kg/d), T2DM rats subjected to combined Dapa treatment and AE (DMDa+AE), and the standard control group (CON). Blood and skeletal muscle samples were collected after 6 weeks of intragastric administration and treadmill exercise. The results showed that DMDa monotherapy could reduce the accumulation of white adipose tissue and skeletal muscle lipid droplets and improve HOMA-IR. While the combined AE led to further reductions in subcutaneous white adipose tissue and fasting glucose levels, it did not confer additional benefits in terms of HOMA-IR. Furthermore, Dapa monotherapy enhanced skeletal muscle mitochondrial biogenesis (PGC-1α, NRF1, TFAM, and COX IV), mitochondrial dynamics (OPA1, DRP1, and MFN2), and mitophagy (PGAM5 and PINK1) related protein levels. Nevertheless, the combination of Dapa with AE treatment did not yield an additive effect. In conclusion, this study highlights the potential of SGLT2 inhibitors, specifically Dapa, in ameliorating IR and maintaining MQC in skeletal muscle in rats with T2DM. However, combined AE did not produce an additive effect, indicating the need for further research.

Abstract The collision between India and Eurasia mobilizes multiple processes of continental tectonics. However, how deformation develops within the lithosphere across the Tibetan Plateau is still poorly known and a synoptic view is missing. Here, we exploit an extensive geodetic observatory to resolve the kinematics of this diffuse plate boundary and the arrangement of various mechanisms down to upper-mantle depths. The three-dimensional velocity field is compatible with continental underthrusting below the central Himalayas and with delamination rollback below the western syntaxis. The rise of the Tibetan Plateau occurs by shortening in the Indian and Asian crusts at its southern and northwestern margins. The subsidence of Central Tibet is associated with lateral extrusion and attendant lithospheric thinning aided by the downwelling current from the opposite-facing Indian and Asian collisions. The current kinematics of the Indian-Eurasian collision may reflect the differential evolution of the inner and outer Tibetan Plateau during the late Cenozoic.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Solar-driven hydrogen evolution coupled with organic synthesis is important but challenging. Here, the authors report an in-situ oxygen impregnation strategy to build a ruthenium-based amorphous hybrid-mixture with abundant atomic interfaces and show efficient hydrogen evolution with small molecule oxidation.

Partial discharge (PD) is the dominant insulating defect in Gas-Insulated Switchgear (GIS). The existing detection methods are mainly divided into built-in wire-connected disk antennas with destructive drilling and external ultra-high frequency antennas with poor anti-interference ability. This research introduces a passive wireless PD sensor implanted inside GIS on the observation window. The sensor is implemented by a sheeting branch-inductor with multiple resonances which is able to enhance detection sensitivity. A coaxially aligned readout circuit, positioned outside the GIS, interrogates the PD sensor to wirelessly obtain the PD signal. The proposed sensing scheme improves signal-to-noise ratio and ensures minimal disruption to the electric field distribution inside GIS. An experimental setup was established in a controlled laboratory environment to benchmark the multi-resonant sensor against the commercial UHF sensor. A 2.5-times enhancement of signal strength was observed. Since our sensor was implanted inside the GIS, a high signal-to-noise ratio (68.82 dB) was obtained. Moreover, we constructed a wireless calibration test to investigate the accuracy of the proposed sensor. The precision of the signal test was as high as 0.72 pC. The pulse phase distribution information was collected to demonstrate a phase-resolved partial discharge (PRPD) pattern. The experiment results validate the effectiveness of the proposed method and demonstrate excellent performance in PD detection.