Intrinsically Microporous Polyimides Derived from 2,2'-Dibromo-4,4',5,5'-bipohenyltetracarboxylic Dianhydride for Gas Separation Membranes.

This work aims to expand the structure-property relationships of bromo-containing polyimides and the influence of bromine atoms on the gas separation properties of such materials. A series of intrinsically microporous polyimides were synthesized from 2,2'-dibromo-4,4',5,5'-bipohenyltetracarboxylic dianhydride (Br-BPDA) and five bulky diamines, (7,7'-(mesitylmethylene)bis(8-methyldibenzo[b,e][1,4]dioxin-2-amine) (MMBMA), 7,7'-(Mesitylmethylene)bis(1,8-dimethyldibenzo[b,e][1,4] dioxin-2-amine) (MMBDA), 4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diamine (TBDA1), 4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-3,9-diamine (TBDA2), and (9R,10R)-9,10-dihydro-9,10-[1,2]benzenoanthracene-2,6-diamine (DAT). The Br-BPDA-derived polyimides exhibited excellent solubility, high thermal stability, and good mechanical properties, with their tensile strength and modulus being 59.2-109.3 MPa and 1.8-2.2 GPa, respectively. The fractional free volumes (FFVs) and surface areas (SBET) of the Br-BPDA-derived polyimides were in the range of 0.169-0.216 and 211-342 m2 g-1, following the order of MMBDA > MMBMA > TBDA2 > DAT > TBDA1, wherein the Br-BPDA-MMBDA exhibited the highest SBET and FFV and thus highest CO2 permeability of 724.5 Barrer. Moreover, Br-BPDA-DAT displayed the best gas separation performance, with CO2, H2, O2, N2, and CH4 permeabilities of 349.8, 384.4, 69.8, 16.3, and 19.7 Barrer, and H2/N2 selectivity of 21.4. This can be ascribed to the ultra-micropores (<0.7 nm) caused by the high rigidity of Br-BPDA-DAT. In addition, all the bromo-containing polymers of intrinsic microporosity membranes exhibited excellent resistance to physical ageing.

Penehyclidine hydrochloride alleviates lung ischemia-reperfusion injury by inhibiting pyroptosis.

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.

Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

Plasma MCP-1 and TGF-ß1 Levels are Associated with Kidney Injury in Children with Congenital Anomalies of the Kidney and Urinary Tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are primarily causal for end-stage renal disease and have significant implications for long-term survival. A total of 39 healthy controls and 94 children with chronic kidney disease (CKD) were enrolled (3-12 years old as children, 13-18 years old as adolescents), who were divided into CAKUT and Non-CAKUT according to the etiology of CKD. CKD group was further classified according to estimating glomerular filtration rate (eGFR). Circulating levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemokine-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were analyzed. The relationship between these inflammatory markers with eGFR and the kidney injury parameter (urine protein) was investigated to assess their potential as early markers of disease progression. All circulating levels of these inflammatory cytokines were increased in CKD patients (including CAKUT and Non-CAKUT) compared with healthy subjects. The circulating levels of MCP-1 and TGF-ß1 were increased in CAKUT adolescents compared with CAKUT children. In CAKUT children, levels of MCP-1 and TGF-ß1 increased as CKD progressed, and MCP-1 and TGF-ß1 were negatively and significantly correlated with eGFR and positively with urine protein. MCP-1 and TGF-ß1 may contribute to the early detection of CKD and disease stage/progression in CAKUT children.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Hollow-microsphere-integrated optofluidic immunochip for myocardial infarction biomarker microanalysis.

This work developed an optofluidic immunochip that uses whispering gallery mode with fiber laser enhancement, for the rapid detection of a key biomarker cardiac troponin I for acute myocardial infarction (AMI). The immunochip adopted an innovative design, using perforated hollow glass microspheres (HGMS) as carriers, with antibodies immobilized on the inner surface of the HGMS, thereby achieving ultra-low sample consumption. The performance of the immunochip was improved by fiber laser, including spectral width compression to 0.019 nm, optical signal-to-noise ratio amplification to 63.17 dB, and an enhancement in the limit of detection to 5 pg/mL. Moreover, this immunochip can provide results within 15 min, making it highly suitable for early AMI risk management. Compared to the standard electrochemiluminescence detection method, although some differences exist in the results of the immunochip due to the principle of detection and differences in antibody affinity, its positive reference value can be calculated as 0.0754 ng/mL, with a successful recognition rate of 88% for positive patients. The immunosensor is integrated on a polydimethylsiloxane substrate, with a compact size suitable for use in point-of-care devices and AMI self-screening, as well as rapid disease screening and microanalysis of various biomarkers, offering new possibilities for applications in these fields.

Effect of sleep deprivation by MMP-WM on rat neurological function and Tau protein in hippocampus.

An in-depth understanding of the pathogenesis and mechanisms of sleep disorders is important for finding reliable treatments and interventions in the future. This study aims to explore the effect of sleep deprivation by modified multiple platform-water maze (MMP-WM) on rat neurological function and Tau protein in the hippocampus, as well as the intervention effect of remimazolam. First, 40 Sprague Dawley (SD) rats were divided into a control group (no treatment), a Rem group (remimazolam), an MMP-WM group (sleep deprivation model in rats established by MMP-WM), and a combined group (MMP-WM + remimazolam). Five rats were randomly selected from each group for behavior tests at 1 d and 7 d of drug administration or sleep deprivation for Morris water maze and open field test. After that, the rats were executed, the hippocampus was isolated for Nissl staining, and the protein expression of phosphorylated Tau (p-Tau) in the CA1 region of the hippocampus was measured by immunohistochemistry. At 1 d, the status in the MMP-WM group was more similar to that in the control group The MMP-WM group showed sparsely arranged hippocampal CA1 neurons, reduced number of Nissl bodies, prolonged escape latency, decreased number of platform crossings and percentage of activity time in the central region, substantially increased p-Tau expression. In contrast, the combined group showed significant improvement in nerve injury, behavior test results, p-Tau at 7 d compared with the MMP-WM group and the same group at 1 d. In addition, detection of brain-derived neurotrophic factor (BDNF) and neurotransmitter levels in the cerebrospinal fluid also showed improved neurologic function in the combined group. These results confirm tha MMP-WM was effective in the establishment of sleep deprivation rat model that accurately reflects the pathological manifestations of sleep disorders in human, and the use of remimazolam effectively reversed the pathological damage in sleep-deprived rats.

m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a hematological malignancy with high metabolic heterogeneity. N6-methyladenosine (m6A) modification plays an important role in metabolism through regulating circular RNAs (circRNAs). However, the underlying mechanism is not yet fully understood in CLL. Herein, an m6A scoring system and an m6A-related circRNA prognostic signature are established, and circTET2 as a potential prognostic biomarker for CLL is identified. The level of m6A modification is found to affect the transport of circTET2 out of the nucleus. By interacting with the RNA-binding protein (RBP) heterogeneous nuclear ribonucleoprotein C (HNRNPC), circTET2 regulates the stability of CPT1A and participates in the lipid metabolism and proliferation of CLL cells through mTORC1 signaling pathway. The mTOR inhibitor dactolisib and FAO inhibitor perhexiline exert a synergistic effect on CLL cells. In addition, the biogenesis of circTET2 can be affected by the splicing process and the RBPs RBMX and YTHDC1. CP028, a splicing inhibitor, modulates the expression of circTET2 and shows pronounced inhibitory effects. In summary, circTET2 plays an important role in the modulation of lipid metabolism and cell proliferation in CLL. This study demonstrates the clinical value of circTET2 as a prognostic indicator as well as provides novel insights in targeting treatment for CLL.

Reaction dynamics for the Cl(2P) + XCl → XCl + Cl(2P) (X = H, D, Mu) reaction on a high-fidelity ground state potential energy surface.

In this work, the dynamics of a prototypical heavy-light-heavy abstract reaction, Cl(2P) + HCl → HCl + Cl(2P), is investigated both by constructing a new potential energy surface (PES) and by rate coefficient calculations. Both the permutation invariant polynomial neural network method and the embedded atom neural network (EANN) method, based on ab initio MRCI-F12+Q/AVTZ level points, are used for obtaining globally accurate full-dimensional ground state PES, with the corresponding total root mean square error being only 0.043 and 0.056 kcal/mol, respectively. In addition, this is also the first application of the EANN in a gas-phase bimolecular reaction. The saddle point of this reaction system is confirmed to be nonlinear. In comparison with both the energetics and rate coefficients obtained on both PESs, we find that the EANN is reliable in dynamic calculations. A full-dimensional approximate quantum mechanical method, ring-polymer molecular dynamics with a Cayley propagator, is employed to obtain the thermal rate coefficients and kinetic isotopic effects of the title reaction Cl(2P) + XCl→ XCl + Cl(2P) (H, D, Mu) on both new PESs, and the kinetic isotope effect (KIE) is also obtained. The rate coefficients reproduce the experimental results at high temperatures perfectly but with moderate accuracy at lower temperatures, but the KIE is with high accuracy. The similar kinetic behavior is supported by quantum dynamics using wave packet calculations as well.

First-principles surface reaction rates by ring polymer molecular dynamics and neural network potential: role of anharmonicity and lattice motion.

Elementary gas-surface processes are essential steps in heterogeneous catalysis. A predictive understanding of catalytic mechanisms remains challenging due largely to difficulties in accurately characterizing the kinetics of such steps. Experimentally, thermal rates for elementary surface reactions can now be measured using a novel velocity imaging technique, providing a stringent testing ground for ab initio rate theories. Here, we propose to combine ring polymer molecular dynamics (RPMD) rate theory with state-of-the-art first-principles-determined neural network potential to calculate surface reaction rates. Taking NO desorption from Pd(111) as an example, we show that the harmonic approximation and the neglect of lattice motion in the commonly-used transition state theory overestimates and underestimates the entropy change during the desorption process, respectively, leading to opposite errors in rate coefficient predictions and artificial error cancellations. Including anharmonicity and lattice motion, our results reveal a generally neglected surface entropy change due to significant local structural change during desorption and obtain the right answer for the right reasons. Although quantum effects are found to be less important in this system, the proposed approach establishes a more reliable theoretical benchmark for accurately predicting the kinetics of elementary gas-surface processes.

Model experiment research on HPTL anchoring technology for coal-rock composite roof in deep roadway.

Since the western region of China, which is typical of extraordinary resource endowments, has gradually emerged as the major mining zone in China, the mining of thick coal seams and roadways with coal-rock composite roof have become more and more common in this region. However, it is extremely difficult to realize safe and effective maintenance and control of such roadways due to the differences in natural endowments of coal-rock masses. With the roadway with coal-rock composite roof of Hulusu Coal Mine in western China as the engineering background, experiment research on large-scale similarity model was conducted through comprehensive measures such as the pneumatic loading system, the surrounding rock stress monitoring system, the roadway deformation monitoring system, the bolt load monitoring system, and the displacement field monitoring system in this paper. According to the results of the experiment, the control effects of the three support systems on the roadway with coal-rock composite roof were significantly different. When the single support of short anchor bolts was applied, the comparatively low initial anchor-hold failed to constrain the initial micro deformation of the roof. Consequently, wide-range fractures of the roof were triggered at a loading pressure of 0.8 MPa. In the meanwhile, the deep surrounding rocks witnessed a downward inflection point in stress, accompanied by the possibility of the collapse of the thin-layer anchorage zone at any time. As for the support combining both short anchor bolts and long anchor cables, though a reinforced effect on the bolt anchorage zone could be achieved with the help of the cables, the active reinforcement capacity of the bolt was limited. The bolt anchorage zone was the first to be damaged at a loading pressure of 0.9 MPa, which would subsequently affect the effective bearing capacity of the deep surrounding rocks. In the application of the single support of high-strength long anchor bolts, the long bolts with high pre-tightening force were able to lock multiple groups of coal-rock strata to form a thick-layer anchorage bearing structure capable of withstanding a load as high as 1.0 MPa. The crash and collapse of the coal wall eventually caused the subsidence of the roof. Based on the intense dynamic load experiment and the feedbacks of engineering application outcomes in the field, it was concluded that the high-pretension thick-layer (HPTL) anchoring technology can effectively constrain the deformation of roadways with coal-rock composite roof with favorable application outcomes.

Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives.

ABSTRACT: The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

Early Guideline-Directed Medical Therapy and in-Hospital Major Bleeding Risk in ST-Elevation Myocardial Infarction Patients Treated with Percutaneous Coronary Intervention: Findings from the CCC-ACS Project.

PURPOSE: Previous reports demonstrated a bleeding avoidance potential of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and ß-blocker. It remains unclear whether early guideline-directed medical therapy [GDMT, i.e., the combined use of ß-blocker, angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and statin] confers protection against bleeding in the setting of high-intensity antithrombotic therapy. METHODS: We assessed associations between the use of early (within the first 24 h) GDMT and in-hospital major bleeds, ischemic events and mortality among ST-elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. RESULTS: Among 34,538 STEMI patients without contra-indications to GDMT and eligible for analysis, 35.5% received early GDMT. In a 1-to-2 propensity-score matched cohort, compared with non-early GDMT, early GDMT was associated with a 25% reduction in major bleeds [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60-0.94], with parallel reductions in ischemic events (OR 0.60, 95%CI 0.45-0.78) and in-hospital mortality (OR 0.43, 95%CI 0.31-0.61). Early GDMT-associated reduction in major bleeds was generally consistently observed across different major bleeding definitions and in sensitivity analyses. Additionally, no significant interaction was observed in subgroup analyses. CONCLUSION: In a large nationwide registry, early initiation of GDMT was associated with reduced risk for in-hospital major bleeds in STEMI patients treated with PCI. To improve the outcome of STEMI, further effort should be made to reinforce the early use of GDMT in this patient population.

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project.

PURPOSE: Thrombus aspiration in ST-elevation myocardial infarction (STEMI) with high thrombus burden did not improve clinical outcomes. The clinical efficacy of the bailout use of platelet glycoprotein IIb/IIIa inhibitors (GPIs) in this clinical scenario remains unknown. METHODS: We assessed associations between GPI use and in-hospital major bleeds, ischemic events, and mortality among STEMI patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration in a nationwide acute coronary syndrome registry (the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project). RESULTS: A total of 5896 STEMI patients who received thrombus aspiration were identified, among which 56.3% received GPI therapy. In a 1-to-1 propensity-score-matched cohort, compared with STEMI patients not treated with GPI, GPI use was associated with a 69% increase in major in-hospital bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on mortality (OR: 0.93, 95% CI: 0.55 to 1.58). However, among patients aged < 60 years, GPI use was associated with a reduction in ischemic events (OR: 0.27, 95% CI: 0.08 to 0.98), and no significant increase in major bleeds was observed. CONCLUSION: In a nationwide registry, routine use of GPI following thrombus aspiration was not associated with reduced in-hospital ischemic events and mortality but at the cost of increased major bleeding. However, for patients aged < 60 years, there may be a potential net benefit.

Complete response to sotorasib as neoadjuvant treatment in patient with locally advanced primary pulmonary sarcoma harboring KRAS mutation: a case report.

Background: Primary pulmonary sarcoma (PPS) is very rare relative to other subtypes of lung cancer. Therefore, evidence-based treatment options for PPS patients have remained unclear. Identification of actionable cancer driver mutations in patients with non-small cell lung cancer (NSCLC) has provided the chance to use targeted treatments and improve patient clinical outcomes. In addition to epidermal growth factor receptor (EGFR), the wide use of high-throughput genomic profiling with next-generation sequencing (NGS) has also identified other cancer driver genes such as Kirsten rat sarcoma (KRAS), human epidermal growth factor receptor 2 (HER2), and mesenchymal epithelial transition (MET). Case Description: In our study, we reported a locally advanced PPS patient harboring KRAS G12C mutation. The clinical stage before neoadjuvant treatment was stage IIIB (c.T3N2M0). The direct KRAS G12C inhibitor sotorasib (AMG-510) was used as neoadjuvant treatment and the patient achieved complete response (CR). Then, the patient underwent video-assisted thoracoscopic surgery (VATS) with reserved spontaneous breathing for surgical resection. The pathological evaluation was indicative of pathological CR (pCR). Further follow-ups are required to evaluate the long-term clinical benefit of neoadjuvant treatment with sotorasib and surgical resection with VATS. Conclusions: To our knowledge, it was the first study to use sotorasib for a PPS patient harboring KRAS G12C mutation in a neoadjuvant setting. Further follow-ups are required to evaluate the long-term clinical benefit of neoadjuvant treatment with sotorasib and surgical resection with VATS.

Field measurement of local wind environment on the approach deck of a suspension bridge in mountain terrain.

The local wind environment above the bridge deck affects the aerodynamic characteristics of vehicles, thus affecting the driving safety of the bridge deck. Influenced by the mountain topography and the bridge deck's ancillary facilities, the local wind environment above the bridge deck is complex and changeable, and its impact on the bridge deck traffic can not be ignored. In order to accurately evaluate the local wind field parameters, a monitoring system of the local wind environment is developed. Utilizing the monitoring system, wind parameters above the approach deck of a long-span suspension bridge in a mountain area are measured. The relationship of wind characteristics between the incoming flow and the wind above the bridge deck is investigated. Results show the significant difference between the local wind environment above the bridge deck and the incoming flow's characteristics; the wind profile above the bridge deck does not follow the exponential distribution; the equivalent height of the wind load on the vehicle is higher than the vehicle's gravity centre. This study is relevant for studying the local wind environment, driving safety, and serviceability of long-span bridges in mountainous areas.

New Stable and Fast Ring-Polymer Molecular Dynamics for Calculating Bimolecular Rate Coefficients with an Example of OH + CH4.

The accurate and efficient calculation of the rate coefficients of chemical reactions is a key issue in the research of chemical dynamics. In this work, by applying the dimension-free ultrastable Cayley propagator, the thermal rate coefficients of a prototypic high dimensional chemical reaction OH + CH4 → H2O + CH3 in the temperature range of 200 to 1500 K are investigated with ring polymer molecular dynamics (RPMD) on a highly accurate full-dimensional potential energy surface. Kinetic isotope effects (KIEs) for three isotopologues of the title reaction are also studied. The results demonstrate excellent agreement with experimental data, even in the deep tunneling region. Especially, the Cayley propagator shows a high calculation efficiency with little loss of accuracy. The present results confirmed the applicability of the RPMD method, particularly the speed-up using a Cayley propagator, in theoretical calculations of bimolecular reaction rates.

Early Statin Therapy and In-Hospital Outcomes in Acute Coronary Syndrome Patients Presenting with Advanced Killip Class at Admission: Findings from the CCC-ACS Project.

PURPOSE: It is unknown if acute coronary syndrome (ACS) patients presenting with advanced Killip class (III/IV) would benefit from early statin therapy. Therefore, we aimed to explore the relationship between statin therapy within the first 24 h of medical contact and in-hospital outcomes in this patient population in a nationwide registry. METHOD: In the Improving Care for Cardiovascular Disease in China-ACS project, among ACS patients presenting with Killip class III/IV, we performed the following three analyses: (i) the associations between early statin therapy and risks for in-hospital mortality and ischaemic events; (ii) the dose effect of statins on mortality and (iii) the interaction between low-density lipoprotein cholesterol (LDL-C) levels and statins on mortality. RESULT: Among 104,516 ACS patients, 12,149 presented with advanced Killip class and 89.3% received early statins. Multivariable-adjusted logistic regression models revealed a 69% reduction in mortality in the statin group (adjusted odds ratio [OR] 0.31; 95% confidence interval [CI] 0.25-0.39), parallel with a reduction in ischaemic events (adjusted OR 0.50, 95% CI 0.33-0.74), compared with those not receiving early statins, which was consistent in multiple sensitivity analyses. Additionally, the protective association of early statins on in-hospital mortality was observed even among patients that received a low-to-moderate dose. Finally, the short-term survival benefit of early statins was independent of LDL-C. CONCLUSION: In a nationwide ACS registry, statin therapy initiated within the first 24 h of medical contact was associated with a reduced risk of in-hospital mortality in ACS patients presenting with advanced Killip class.

Expression Regulation of Water Reabsorption Genes and Transcription Factors in the Kidneys of Lepus yarkandensis.

Lepus yarkandensis is a desert-dwelling animal that has various adaptations to cope with drought. The kidney maintains water and acid-base balance mainly through the vasopressin-regulated water reabsorption pathway and proximal tubular bicarbonate reabsorption pathway. In this study, we compared the differentially expressed genes (DEGs) and transcription factors in the kidneys of L. yarkandensis and Oryctolagus cuniculus to explore the relationship between the DEGs in kidneys and the animals' adaptations. Transcriptome sequencing data were used to predict the differentially-expressed water reabsorption genes and their transcription factors. Quantitative real-time PCR, immunohistochemistry, and western blotting were used to detect and verify the expression of DEGs in the kidney at mRNA and protein levels. Transcriptome analysis of the kidney of L. yarkandensis and O. cuniculus showed that 6,610 genes were up-regulated and 5,727 genes down-regulated in data shared by both species. According to the data, 232 transcription factors and their corresponding target genes were predicted, from which genes and transcription factors related to renal water reabsorption were screened. Quantitative RT-PCR results showed AQP1, AQP2, ADCY3, HIF1A, CREB3, and NFATc1 had higher expression in the L. yarkandensis kidney; in comparison, FXYD2 mRNA expression levels were lower. In western blotting, transcription factors HIF1A, NFATc1, NF-κB1, and critical genes ADCY3, ATPA1, and SLC4A4, were highly expressed in the kidneys of L. yarkandensis. Immunohistochemical results showed that the ADCY3 protein was in the basolateral membrane of the collecting duct, the ATP1A1 protein was in the basolateral membrane and medulla of proximal tubules, and the SLC4A4 protein was in the basolateral membrane of proximal tubules. According to these results can be inferred that HIF1A, NFATc1, and NF-κB1 play a certain role in regulating the expression of genes related to water reabsorption in the kidney of L. yarkandensis, thus improving the water reclamation efficiency of L. yarkandensis, so as to adapt to the arid desert environment.