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Background Increased vascular CaV1.2 channel function causes enhanced arterial tone during hypertension. This is mediated by elevations in angiotensin II/protein kinase C signaling. Yet, the mechanisms underlying these changes are unclear. We hypothesize that α1C phosphorylation at serine 1928 (S1928) is a key event mediating increased CaV1.2 channel function and vascular reactivity during angiotensin II signaling and hypertension. Methods and Results The hypothesis was examined in freshly isolated mesenteric arteries and arterial myocytes from control and angiotensin II‐infused mice. Specific techniques include superresolution imaging, proximity ligation assay, patch‐clamp electrophysiology, Ca2+ imaging, pressure myography, laser speckle imaging, and blood pressure telemetry. Hierarchical “nested” and appropriate parametric or nonparametric t test and ANOVAs were used to assess statistical differences. We found that angiotensin II redistributed the CaV1.2 pore‐forming α1C subunit into larger clusters. This was correlated with elevated CaV1.2 channel activity and cooperativity, global intracellular Ca2+ and contraction of arterial myocytes, enhanced myogenic tone, and altered blood flow in wild‐type mice. These angiotensin II‐induced changes were prevented/ameliorated in cells/arteries from S1928 mutated to alanine knockin mice, which contain a negative modulation of the α1C S1928 phosphorylation site. In angiotensin II‐induced hypertension, increased α1C clustering, CaV1.2 activity and cooperativity, myogenic tone, and blood pressure in wild‐type cells/tissue/mice were averted/reduced in S1928 mutated to alanine samples. Conclusions Results suggest an essential role for α1C S1928 phosphorylation in regulating channel distribution, activity and gating modality, and vascular function during angiotensin II signaling and hypertension. Phosphorylation of this single vascular α1C amino acid could be a risk factor for hypertension that may be targeted for therapeutic intervention.

Abstract The remarkable successes of graphene have sparked increasing interest in elemental two‐dimensional (2D) materials, also referred to as Xenes. Due to their chemical simplicity and appealing physiochemical properties, Xenes have shown particular potential for numerous (opto) electronic, iontronic, and energy applications. Among them, layered α‐phase tellurene has demonstrated the most promise, thanks to the recent successes in the chemical synthesis of highly crystalline 2D tellurene. However, the general electronic and electrochemical properties of tellurene in electrolyte systems remain ambiguous, hindering their further development. In this work, we studied the electrostatic gating, electrocatalysis, and electrochemical stability of tellurene in electrolyte systems. Our results show that tellurene obtained from both hydrothermal and chemical vapor deposition methods, two mainstream synthetic approaches for Xenes, demonstrates thickness‐dependent ambipolar transport with high hole mobility and stability in both aqueous electrolytes and ionic liquids. More importantly, the electrochemical properties of tellurene are investigated via the emerging on‐chip electrochemistry. Pristine tellurene demonstrates hydrogen evolution reaction with low Tafel slopes and remarkable electrochemical stability in acidic electrolytes over a large potential window. Our study provides a comprehensive understanding of the iontronic and electrochemical properties of tellurene, paving the way for the broad adoption of Xenes in sensors, synaptic devices, and electrocatalysis.

Abstract To determine the optimal temperature in rearing of fry stream groupers, Acrossocheilus fasciatus, a total of 540 fry fish with an initial body weight of (0.57 ± 0.16) g, and body length of (4.08 ± 0.40) cm were randomly distributed to 18 15‐L tanks and reared at six different temperatures (12, 16, 20, 24, 26, and 28°C) for a period of 60 days. Fish were hand‐fed to satiation under all six different temperature treatments. At the end of the experiment, almost all the growth, feeding, and gonadal development parameters were higher in the 26°C group than in the rest of the groups. As temperature increased from 12 to 26°C, the specific growth rate and feeding efficiency of fry significantly increased (p 0.05). In conclusion, increases in temperature significantly improved the growth rate, feeding performance, and gonadal development rate of fry A. fasciatus. Regression analysis based on growth and feeding performance showed that the optimal temperature of rearing fry A. fasciatus was 23.81–26.57°C.

Abstract Background The development of immune checkpoint inhibitors has made a significant breakthrough in the treatment of non‐small‐cell lung cancer (NSCLC). However, there remains a huge unmet clinical need for patients with acquired resistance after initial treatment response. Methods This study evaluated the combination of IBI310 (an anti‐cytotoxic T lymphocyte‐associated antigen‐4 [CTLA‐4] antibody) and sintilimab (an anti‐programmed death 1 [PD‐1]) antibody) in NSCLC patients who have previously been treated with anti‐PD‐1/ligand (L)1 and acquired resistance. The patients were randomly assigned to receive either a lower dose of IBI310 (1 mg/kg Q3W, cohort A) or a higher dose of IBI310 (3 mg/kg Q3W, cohort B) in combination with sintilimab (200 mg Q3W). The primary endpoints of the study were objective response rate (ORR) assessed by RECISTv1.1 and safety, while secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS). Results As of November 2, 2023, the study had enrolled 30 patients, with 15 patients in each cohort. The ORR was 13.3% (2/15, 95% confidence interval [CI], 1.7–40.5) in cohort B. DCR were 46.7% (95% CI, 21.3–73.4) and 66.7% (95% CI, 38.4–88.2) in cohorts A and B, respectively. In cohorts A and B of this trial, the median follow‐up times were 4.2 and 5.6 months, respectively. Median PFS was 1.45 (95% CI, 1.35–2.73) versus 2.73 (95% CI, 1.41–4.90) months for cohort A versus B; the median OS was 7.03 (95% CI, 3.09–not calculable [NC]) months in cohort A and 8.90 (95% CI, 5.13–NC) months in cohort B. Of the 30 patients, 86.7% in both cohorts experienced treatment‐related adverse events (TRAEs) with Grade ≥3 TRAEs occurring in 40% and 53.3% of patients in cohorts A and B, respectively. Conclusion IBI310 3 mg/kg Q3W plus sintilimab was effective in a small number of previously treated anti‐PD‐1/L1‐resistant NSCLC patients.

Abstract Based on the predigestion of the dynamic model of the intelligent firefighting vehicle, a linear 2‐DOF lateral dynamic model and a preview error model are established. To solve the problems of a highly non‐linear vehicle model, time‐varying parameters, output chattering, and poor robustness, the Radial Basis Function neural network sliding mode controller is designed. Then, different driving speeds are used to conduct simulation tests under standard double‐shifting and smooth curve road conditions, and the simulation results are used to analyse the tracking effect of the lateral motion controller on the desired path. The simulation results reveal that the controller designed has high accuracy in tracking the desired path and has good robustness to the disturbance of intelligent firefighting vehicle speed changes.

Abstract Colon adenocarcinoma (COAD) has a high incidence and death rate. Despite the fact that change in fatty acid metabolism promotes tumor growth and metastasis to the greatest degree among metabolite profiles, a thorough investigation on the involvement of fatty acid metabolism‐related genes (FAMRGs) in COAD has yet not been conducted. Here, the clinical data as well as the gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) database. Based on the FAMRG expression data and clinical information, a FAMRG risk signature was developed using LASSO as well as multivariate and univariate Cox regression analyses. Then, the nomogram was used to create a customized prognostic prediction model, and the calibration and receiver operating characteristic curves were used to evaluate the nomogram's prediction performance and discriminative capability. Lastly, a number of studies were conducted to assess the influence of independent FAMRGs on COAD, including unsupervised cluster analysis, functional analysis, and drug sensitivity analysis. Three hundred and sixty‐seven patients were included in this study, and a 12‐FAMRG risk signature was discovered in the training cohort based on a detailed examination of the FAMRGs expression data and clinical information. After that, risk scores were computed to classify patients into low or high‐risk groups, and the Kaplan–Meier curve analysis revealed that patients in the low‐risk group exhibited an elevated overall survival (OS) rate. The FAMRG was shown to be substantially correlated with prognosis in multivariate Cox regression analysis and was validated using the validation dataset. Then, using the clinical variables and risk signature, we developed and validated a prediction nomogram for OS. Functional characterization showed a strong correlation between this signature and immune cell infiltration and immune modulation. Additionally, by evaluating the GDSC database, it was determined that the high‐risk group exhibited medication resistance to many chemotherapeutic and targeted medicines, including VX.680, gemcitabine, doxorubicin, and paclitaxel. Overall, we have revealed the significance of a FAMRG risk signature for predicting the prognosis and response to immunotherapy in COAD, and our findings might contribute to an enhanced comprehension of metabolic pathways and the future development of innovative COAD therapeutic methods.

Abstract Frailty refers to a decline in the physiological functioning of one or more organ systems. It remained unclear whether variations in the trajectory of frailty over time were associated with subsequent cognitive change. The aim of the current study was to investigate the association between frailty trajectories and subsequent cognitive decline based on the Health and Retirement Study (HRS). A total of 15,454 participants were included. The frailty trajectory was assessed using the Paulson–Lichtenberg Frailty Index, while the cognitive function was evaluated using the Langa–Weir Classification. Results showed that severe frailty was significantly associated with the subsequent decline in cognitive function (β [95% CI] = −0.21 [−0.40, −0.03], p = 0.03). In the five identified frailty trajectories, participants with mild frailty (inverted U‐shaped, β [95% CI] = −0.22 [−0.43, −0.02], p = 0.04), mild frailty (U‐shaped, β [95% CI] = −0.22 [−0.39, −0.06], p = 0.01), and frailty (β [95% CI] = −0.34 [−0.62, −0.07], p = 0.01) were all significantly associated with the subsequent cognition decline in the elderly. The current study suggested that monitoring and addressing frailty trajectories in older adults may be a critical approach in preventing or mitigating cognitive decline, which had significant implications for healthcare.

Abstract Building alterations often occur when the buildings ought to be updated to meet new standards. In such processes, original values of existing buildings tend to be neglected in favor of speed and economic benefits from aggressive alterations. In this research, we investigate the mechanism of architectural alterations that respect the value of existing buildings. The research helps uncover the lasting values of buildings that can be preserved in spite of the need for physical adjustments.

This study focuses on a differential wheeled robot’s (DWR) prescribed-time fractional order position control. Firstly, based on the kinematic model of DWR, a distance-related orientation error is designed using the inverse sine function. Based on this, an improved linear velocity constraint function is proposed. Compared with existing methods, while ensuring the correlation between velocity and orientation error, the multibalance point risk caused by large angle errors is avoided. Then, a prescribed-time fractional order position controller based on a time-varying scaling function is proposed to stabilize the kinematic system of DWR in the prescribed time. This controller can stabilize the position control system of the DWR in a prescribed time by adjusting the prescribed-time parameter, avoiding the infinite gain risk in traditional prescribed-time controllers. Finally, through numerical simulation, we verify that the proposed control law can converge the system status of DWR to the bounded interval in the prescribed time.

Abstract Purpose To discuss whether the dome or anterior wall of bladder adenocarcinoma (BAC) should be classified into urachal carcinoma (UrC) and the relationship of primary tumor location (PTL) as well as treatment with survival. Methods Surveillance, Epidemiology, and End Results 18 database was examined for eligible patients from 1975 to 2016. Patients were classified into adenocarcinoma originating from the urachus (UAC), the dome (D‐BAC), the anterior wall (A‐BAC), and the other sites adenocarcinoma of the bladder (O‐BAC). The clinicopathological features, treatment, and survival were compared among the groups. Results Comparable clinicopathologic features were obtained between UAC and D‐BAC, which were different from those of A‐BAC and O‐BAC; otherwise, the latter two had similar clinicopathologic features. Univariable and multivariable Cox regression analyses indicated that PTL was an independent predictor for survival. O‐BAC conferred the worst prognosis then followed by A‐BAC, D‐BAC, and UAC. For non‐metastatic UAC or D‐BAC, partial cystectomy (with an en bloc resection of the urachus and umbilicus) is optimal for survival. However, the worse survival of non‐metastatic D‐BAC (compared with UAC) suggested different modalities, maybe more intensive surgery approaches, should be considered for D‐BAC. Conclusion This study illustrates that PTL of UAC and BAC was an independent predictor for survival. A‐BAC had comparable characters and prognosis with O‐BAC and should not be classified into and treated as UrC. For non‐metastatic disease, non‐metastatic D‐BAC may need more intensive modality.

Abstract Background To compare the efficacy of first‐line bevacizumab plus chemotherapy with cetuximab plus chemotherapy based on the stratification of metastatic colorectal cancer (mCRC) patients with mucinous adenocarcinoma (MA) or mucinous component (MC). Methods A retrospective study involving all mCRC patients receiving first‐line bevacizumab‐based or cetuximab‐based chemotherapy at our hospital from September 2013 to January 2020 was conducted. Overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) were compared between the cetuximab‐chemotherapy group and the bevacizumab‐chemotherapy group on the basis of the conventional pathological classification of MA or MC. Results A total of 620 patients with mCRC were included in our study, consisting of 141 (22.7%) patients with MA/MC and 479 (77.3%) patients with non‐mucinous adenocarcinoma (NMA). In the MA/MC cohort, patients who were treated with bevacizumab‐based chemotherapy were associated with significantly better OS than those treated with cetuximab‐base chemotherapy (30.0 vs. 26.3 months, p = 0.002), irrespective of tumor sites. The efficacy of bevacizumab‐based chemotherapy was higher in nearly all subgroups as shown in the subgroup analysis. In the NMA cohort, median OS was better in the cetuximab plus chemotherapy group than that in the bevacizumab plus chemotherapy group (32.2 vs. 27.0 months, p = 0.005) for left‐side mCRC patients, whereas OS was significantly longer in the bevacizumab plus chemotherapy group for right‐side mCRC patients (26.0 vs. 20.9 months, p = 0.013). Conclusion Conventional pathological classification (e.g. MA/MC) should be considered when tailoring the individualized optimal treatment for mCRC. Bevacizumab plus chemotherapy as first‐line therapy may be the optimal option for patients with MA/MC.

Abstract Mesenchymal stromal cells (MSCs) are essential elements of the bone marrow (BM) microenvironment, which have been widely implicated in pathways that contribute to leukemia growth and resistance. Recent reports showed genotypic and phenotypic alterations in leukemia patient‐derived MSCs, indicating that MSCs might be educated/reprogrammed. However, the results have been inconclusive, possibly due to the heterogeneity of leukemia. Here, the authors report that acute myeloid leukemia (AML) induces MSCs towards an adipogenic differentiation propensity. RNAseq analysis reveal significant upregulation of gene expression enriched in the adipocyte differentiation process and reduction in osteoblast differentiation. The alteration is accompanied by a metabolic switch from glycolysis to a more oxidative phosphorylation‐dependent manner. Mechanistic studies identify that AML cell‐derived exosomes play a vital role during the AML cell‐mediated MSCs education/reprogramming process. Pre‐administration of mice BM microenvironment with AML‐derived exosomes greatly enhance leukemia engraftment in vivo. The quantitative proteomic analysis identified a list of exosomal protein components that are differently expressed in AML‐derived exosomes, which represent an opportunity for novel therapeutic strategies based on the targeting of exosome‐based AML cells‐MSCs communication. Collectively, the data show that AML‐educated MSCs tend to differentiate into adipocytes contributing to disease progression, which suggests complex interactions of leukemia with microenvironment components.

Abstract As an important category of porous crystalline materials, metal‐organic frameworks (MOFs) have attracted extensive research interests owing to their unique structural features such as tunable pore structure and enormous surface area. Besides controlling the size, dimensionality, and composition of MOFs, further exploring the crystal‐phase‐dependent physicochemical properties is essential to improve their performances in various applications. Recently, great progress has been achieved in the phase engineering of nanomaterials (PEN), which provides an effective strategy to tune the functional properties of nanomaterials by modulating the arrangement of atoms. In this review, we adopt “phase” instead of “topology” to describe the crystal structure of MOFs and summarize the recent advances in phase engineering of MOFs. The two main strategies used to control the phase of MOFs, that is, phase‐controlled synthesis and phase transformation of MOFs, will be highlighted. The roles of various reaction parameters in controlling the crystal phase of MOFs are discussed. Then, the phase dependence of MOFs in various applications including luminescence, adsorption, and catalysis are introduced. Finally, some personal perspectives about the challenges and opportunities in this emerging field are presented.

The biological mechanisms linking diet-related obesity and autistic behaviors remain unclear. Metformin has proven to be beneficial in the treatment of many syndromes, including autism spectrum disorder. Therefore, the aim of this study was to assess whether metformin treatment could ameliorate metabolic and behavioral alterations in C57BL/6 mice kept on a high-fat diet (HFD), and whether these changes were related to modifications in the gut microbiota and 5-HT levels. As expected, ten weeks of HFD ingestion increased body weight, adiposity, and glucose levels. HFD-fed mice showed a marked aggravation of repetitive behaviors (marble burying and self-grooming), and this was prevented by metformin administration. In addition, HFD-fed mice increased the total distance travelled in the open field test. This hyperactivity was counteracted by metformin cotreatment. In the elevated plus maze test, HFD-fed mice showed a reduced number of entries into the open arms. Interestingly, both HFD and metformin cotreatment increased social interactions in the three-chamber test. HFD increased the levels of intestinal tryptophan and 5-hydroxyindoleacetic acid. Metformin stimulated gut tryptophan and promoted the synthesis of 5-HT in the HFD group. Lactococcus, Trichococcus, Romboutsia, and Faecalibaculum were enriched in HFD-fed mice, whereas the HFD group cotreated with metformin was enriched in Intestinimonas and L. reuteri. Faecalibacterium was positively correlated with sociability and 5-HT pathway components in mice that received metformin. In summary, HFD consumption elicited a complex phenotype comprising higher levels of anxiety-like and repetitive behaviors but also increased sociability. Metformin could potentially improve HFD-induced disorders in the autistic spectrum through a mechanism involving positive modulation of 5-HT levels in the gut and its microbiota composition.

FanWing has been taken to the visual field because of its performance combination of fixed-wing aircraft and helicopter. Its flight mode is currently limited mainly by a remote control, while the research of automated flight control is on the rise. The fan wing could offer lift, thrust, and the additional pitch moment for longitudinal control. At the same time, the roll moment and the yaw moment can be generated by the differential rotation of the cross-flow fan to realize the lateral control. It provides the possibility for its emergency flight control when the aerodynamic control becomes inefficient at a low speed. The difficulties in designing the emergency control system in both the longitudinal and lateral controls are analyzed. And it emphasizes the importance of selecting its center of gravity and the emergency control method of longitudinal control in engineering. The simulation results show that as an emergency flight control system, fan wing control is feasible. The study of the fan wing control will provide a reference solution for its further engineering applications.

Abstract Objective To investigate the clinical effects of the mirror neuron system (MNS)‐based training on upper extremity motor function and cognitive function in stroke patients. Methods Sixty stroke patients (time from stroke onset 3–9 months) with upper extremity paresis (Brunnstrom stage II–IV) and cognitive impairment (MoCA score ≥ 15) were enrolled in this study. Patients were randomly allocated into MNS treatment group (N = 30) and control group (N = 30). Both groups underwent regular training for upper extremity motor function and cognitive function, and the MNS group was trained with a therapeutic apparatus named mirror neuron system training (MNST) including different levels of action observation training (AOT). Training lasted 20 min/day, 5 days/week for 8 weeks. MoCA, reaction time, and Wisconsin Card Sorting Test (WCST) were assessed at baseline and 8 weeks after training. Furthermore, Fugl‐Meyer assessment (FMA) and Modified Barthel index (MBI) were adopted to evaluated upper extremity motor function and daily life ability. Results After 8 consecutive weeks’ training, both groups showed significant improvements on the upper extremity motor function, cognitive function, and daily life ability score after training (p

Intestinal ischemia/reperfusion (I/R) injury often causes inflammatory responses and coagulation disorders, which is further promoting the deterioration of the disease. Hydrogen has anti-inflammatory, antioxidative, and antiapoptotic properties against various diseases. However, the effect of hydrogen on coagulation dysfunction after intestinal I/R and the underlying mechanism remains unclear. The purpose of this study was to explore whether hydrogen-rich solution (HRS) could attenuate coagulation disorders and inflammation to improve intestinal injury and poor survival following intestinal I/R. The rat model of intestinal I/R injury was established by clamping the superior mesenteric artery for 90 min and reperfusion for 2 h. HRS (10 or 20 mL/kg) or 20 mL/kg 0.9% normal saline was intravenously injected at 10 min before reperfusion, respectively. The samples were harvested at 2 h after reperfusion for further analyses. Moreover, the survival rate was observed for 24 h. The results showed that HRS improved the survival rate and alleviated serum diamine oxidase activities, intestinal injury, edema, and apoptosis. Interestingly, HRS markedly improved intestinal I/R-mediated coagulation disorders as evidenced by abnormal conventional indicators of coagulation and thromboelastography. Additionally, HRS attenuated inflammatory responses and the elevated tissue factor (TF) and inhibited nuclear factor kappa beta (NF-κB) and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in peripheral blood mononuclear cells. Moreover, inflammatory factors and myeloperoxidase were closely associated with TF level. This study thus emphasized upon the amelioration of coagulation disorders and inflammation by HRS as a mechanism to improve intestinal I/R-induced intestinal injury and poor survival, which might be partially related to inhibition of NF-κB/NLRP3 pathway.

BackgroundHeart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences is poorly understood. Methods and ResultsThis study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3 weeks with angiotensin II to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3 weeks of treatment. RNA sequencing was performed on hearts, and sex differences in mRNA expression at baseline and following hypertrophy were observed, as well as within‐sex differences between baseline and hypertrophy. Sex differences in mRNA were substantial at baseline and reduced somewhat with hypertrophy, as the mRNA differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify mRNA networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on PPARα (peroxisome proliferator‐activated receptor α). Mouse experiments further showed that acute inhibition of PPARα blocked sex differences in the development of hypertrophy. ConclusionsThe data in this study suggest that PPARα is involved in the sex‐dimorphic regulation of cardiac hypertrophy.

Recycling and reusing of poly (ethylene terephthalate) (PET) fabrics waste are essential for reducing serious waste of resources and environmental pollution caused by low utilization rate. The liquid-phase polymerization method has advantages of short process flow, low energy consumption, and low production cost. However, unlike prepolymer, the material characteristics of PET fabrics waste (complex composition, high intrinsic viscosity, and large quality fluctuations) make its recycling a technique challenge. In this study, the falling film-rotating disk combined reactor is proposed, and the continuous liquid-phase polymerization is modeled by optimizing and correcting existing models for the final stage of PET polymerization to improve the product quality in plant production. Through modeling and simulation, the weight analysis of indexes closely related to the product quality (intrinsic viscosity, carboxyl end group concentration, and diethylene glycol content) was investigated to optimize the production process in order to obtain the desired polymer properties and meet specific product material characteristics. The model could be applied to other PET wastes (e.g., bottles and films) and extended to investigate different aspects of the recycling process.

An efficient caged phosphate charring agent named PEPA was synthesized and combined with melamine pyrophosphate (MPP) to flame-retard polypropylene (PP). The effects of MPP/PEPA on the flame retardancy and thermal degradation of PP were investigated by limiting oxygen index (LOI), vertical burning test (UL-94), cone calorimetric test (CCT), and thermogravimetric analysis (TGA). It was found that PEPA showed an outstanding synergistic effect with MPP in flame retardant PP. When the content of PEPA was 13.3 wt% and MPP was 6.7 wt%, the LOI value of the flame retardant PP was 33.0% and the UL-94 test was classed as a V-0 rating. Meanwhile, the peak heat release rate (PHRR), average heat release rate (AV-HRR), and average mass loss rate (AV-MLR) of the mixture were significantly reduced. The flame-retardant and thermal degradation mechanism of MPP/PEPA was investigated by TGA, Fourier transform infrared spectroscopy (FTIR), TG-FTIR, and scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDXS). It revealed that MPP/PEPA could generate the triazine oligomer and phosphorus-containing compound radicals which changed the thermal degradation behavior of PP. Meanwhile, a compact and thermostable intumescent char was formed and covered on the matrix surface to prevent PP from degrading and burning.