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Abstract The orbital Hall effect in light materials has attracted considerable attention for developing orbitronic devices. Here we investigate the orbital torque efficiency and demonstrate the switching of the perpendicularly magnetized materials through the orbital Hall material, i.e., Zr. The orbital torque efficiency of approximately 0.78 is achieved in the Zr orbital Hall material with the perpendicularly magnetized [Co/Pt]3 sample, which significantly surpasses that of the perpendicularly magnetized CoFeB/Gd/CoFeB sample (approximately 0.04). Such a notable difference is attributed to the different spin-orbit correlation strength between the [Co/Pt]3 sample and the CoFeB/Gd/CoFeB sample, confirmed through theoretical calculations. Furthermore, the full magnetization switching of the [Co/Pt]3 samples with a switching current density of approximately 2.6×106 A/cm2 has been realized through Zr, which even outperforms that of the W spin Hall material. Our finding provides a guideline to understand orbital torque efficiency and paves the way for developing energy-efficient orbitronic devices.

Abstract Sotatercept is a breakthrough, first‐in‐class biologic, that is FDA‐approved for the treatment of pulmonary arterial hypertension (PAH). A population pharmacokinetic (PopPK) model was developed using data from two phase 1 studies in healthy participants, and two phase 2 studies and one phase 3 study in participants with PAH. The pooled sotatercept PK data encompassed single intravenous (IV) or subcutaneous (SC) doses ranging from 0.01 to 3.0 mg/kg, as well as multiple SC doses ranging from 0.03 to 1.0 mg/kg, with PK samples collected up to a maximum of ~150 weeks following Q3W and Q4W dosing regimens. The final PopPK analysis included 350 participants, with 30 and 320 participants receiving sotatercept IV and SC, respectively. A two‐compartment model with a first‐order absorption rate constant and a linear disposition from central compartment well‐described sotatercept PK. The estimated bioavailability is ~66%; bioavailability, clearance (CL), and central volume (VC) have low to moderate inter‐individual variability. Time‐varying body weight and baseline albumin concentration were statistically significant predictors of PK; CL and VC were predicted to increase with increasing body weight, while CL was predicted to decrease with increasing baseline albumin concentration. However, the magnitude of covariate effects is not predicted to meaningfully alter the disposition of sotatercept. Altogether, the PopPK modeling results demonstrate favorable PK characteristics (low to moderate variability and typical bioavailability), supporting sotatercept as a SC biological agent for the treatment of patients with PAH.

Abstract Background To clarify the value of gait analysis and its consistency with traditional scoring scales for the evaluation of knee joint function after total knee arthroplasty (TKA). Methods This study included 25 patients with knee osteoarthritis (KOA) who underwent bilateral TKA, and 25 conditionally matched healthy individuals, categorised into the experimental and control groups, respectively. Patients in the experimental group underwent gait analysis and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) evaluation before and 1 year after TKA. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Pearson’s correlation analysis was performed on the gait and WOMAC score data of the experimental group before and after TKA. Results One year after TKA, patients’ gait indices (except gait cycle) were significantly better than before surgery, but significantly worse than that of the control group (P 80%. The WOMAC scores and gait analysis results were significantly correlated before TKA (P

Abstract Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

ABSTRACTA pretreatment experiment of preparing starch syrup with α-amylase and twin-screw extrusion together with broken rice of resistant starch rice was studied. Results showed that the content of reducing sugar in the extrudate was 23.52% when the moisture content of the material was 25%, the screw speed was 210 r/min, the barrel temperature was 85°C, and the addition amount of α-amylase was 90 U/g. The influence of various factors was ranked as follows: material ratio > screw speed > α-amylase addition > barrel temperature. After the extrusion, the contents of starch and resistant starch were not significantly changed, fat content was reduced, and protein and ash contents increased. Starch in the rice was degraded, and the particle structure was destroyed, while the crystal structure changed from type A to type V. Thermodynamic properties and solubility both changed. Rice syrup has a high transparency, good rheology, and a more delicate and soft taste.

ObjectiveThis study aimed to investigate the clinical manifestations and prognosis of lung transplant (LTx) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease (COVID-19) pandemic.MethodsThe research participants were LTx recipients who underwent surgery and were regularly followed up at our center. From 1 December 2022 to 28 February 2023, during the COVID-19 pandemic in China, research participants were interviewed either online or in person. SARS-CoV-2 nucleic acid or self-tested antigens were detected according to accessibility. Diagnosis and treatment were performed according to the Diagnosis and Treatment Plan for COVID-19 (10th edition) issued by the National Health Commission of the People's Republic of China. Hospitalized patients underwent chest imaging examinations, routine blood tests, biomarkers for infection and inflammation, and biochemical tests, all of which were taken and recorded. Data were analyzed to describe the features of COVID-19 in LTx recipients.ResultsIn total, 52 patients were enrolled in this study, comprising 48 men and 4 women, with a mean age of 51.71 ± 11.67 years. By 1 December 2022, the mean survival period was 33.87 ± 25.97 months, of which 84.61% of the patients (44/52) had a survival period longer than 12 months. The SARS-CoV-2 infection rate in these LTx recipients was 82.69% (43/52), with 3.85% (2/52) of the infected recipients being asymptomatic, 50.00% (26/52) of the infected recipients experiencing mild COVID-19, 11.54% (6/52) having moderate COVID-19, and 17.31% (9/52) having severe or critical COVID-19. The mortality rate among severe and critical patients was 66.67% (6/9).ConclusionLTx recipients in this cohort exhibited a notable susceptibility to SARS-CoV-2, with 82.69% of individuals diagnosed with COVID-19. Moreover, the mortality rate among critically ill patients was high.

Summary: Background: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. Methods: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. Findings: Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. Interpretation: Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. Funding: This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).

Summary: Benign prostatic hyperplasia (BPH) occurs when there is an imbalance between the proliferation and death of prostate cells, which is regulated tightly by estrogen signaling. However, the role of G protein-coupled estrogen receptor (GPER) in prostate cell survival remains ambiguous. In this study, we observed that prostates with epithelial hyperplasia showed increased yes-associated protein 1 (YAP) expression and decreased levels of estrogen and GPER. Blocking YAP through genetic or drug interventions led to reduced proliferation and increased apoptosis in the prostate epithelial cells. Interestingly, GPER agonists produced similar effects. GPER activation enhanced the phosphorylation and degradation of YAP, which was crucial for suppressing cell proliferation and survival. The Gαs/cAMP/PKA/LATS pathway, downstream of GPER, transmitted signals that facilitated YAP inhibition. This study investigated the interaction between GPER and YAP in the prostate epithelial cells and its contribution to BPH development. It lays the groundwork for future research on developing BPH treatments.

Abstract Purpose To examine the numbers and characteristics of children affected by asthma exacerbation in Chengdu, China, before and after the COVID-19 pandemic to inform efforts to manage childhood asthma in the post epidemic era. Methods Data were retrospectively collected from children admitted for asthma exacerbation to Chengdu Women and Children’s Central Hospital between January 2017 and December 2022. Rates of hospitalization, ages of the affected children, comorbidities and infections, and relationships between hospitalization and seasonal or environmental factors were examined before and after the epidemic. Results Fewer children were hospitalized for asthma exacerbation, yet more hospitalized children had severe exacerbation after the epidemic than before. Rates of hospitalization varied considerably with time of year, and the timing of peak hospitalizations differed before and after the epidemic. Only before the epidemic, rates of hospitalization for asthma exacerbation were positively correlated with humidity. Infants made up a smaller proportion of hospitalized children after the epidemic than before, with preschool children accounting for most hospitalizations after the epidemic. The proportion of children hospitalized for asthma exacerbation who also had pneumonia was significantly smaller after the epidemic than before. Conversely, the proportion of children hospitalized for asthma exacerbation who also had allergic diseases was significantly greater after the epidemic than before. Conclusion The epidemiology of asthma exacerbation in children changed after the epidemic. Future efforts to manage the condition in the paediatric population should focus on severe asthma exacerbation, prevention and management of allergic diseases, and the influence of meteorological and environmental factors.

ABSTRACTA cornerstone of bacterial molecular biology is the ability to genetically manipulate the microbe under study. Many bacteria are difficult to manipulate genetically, a phenotype due in part to robust removal of newly acquired DNA, for example, by restriction-modification (R-M) systems. Here, we report approaches that dramatically improve bacterial transformation efficiency, piloted using a microbe that is challenging to transform due to expression of many R-M systems, Helicobacter pylori. Initially, we identified conditions that dampened expression of several R-M systems and concomitantly enhanced transformation efficiency. We then identified an approach that would broadly protect newly acquired DNA. We computationally predicted under-represented short DNA sequences in the H. pylori genome, with the idea that these sequences reflect targets of sequence-based surveillance such as R-M systems. We then used this information to modify and eliminate such sites in antibiotic resistance cassettes, creating a “stealth” version. Modifying antibiotic resistance cassettes in this way resulted in significantly higher transformation efficiency compared to non-modified cassettes, a response that was genomic loci independent. Our results suggest that avoiding R-M systems, via modification of under-represented DNA sequences or transformation conditions, is a powerful method to enhance DNA transformation. Our approach to identify under-represented sequences is applicable to any microbe with a sequenced genome.IMPORTANCEManipulating the genomes of bacteria is critical to many fields. Such manipulations are made by genetic engineering, which often requires new pieces of DNA to be added to the genome. Bacteria have robust systems for identifying and degrading new DNA, some of which rely on restriction enzymes. These enzymes cut DNA at specific sequences. We identified a set of DNA sequences that are missing normally from a bacterium’s genome, more than would be expected by chance. Eliminating these sequences from a new piece of DNA allowed it to be incorporated into the bacterial genome at a higher frequency than new DNA containing the sequences. Removing such sequences appears to allow the new DNA to fly under the bacterial radar in “stealth” mode. This transformation improvement approach is straightforward to apply and likely broadly applicable.

The heat dome explains about 55% of the 2021 Western North American high temperatures. The intensity of heat extremes associated with such circulations are increasing faster than background global warming due to soil moisture feedbacks.

The complement system is a key protective response against infectious pathogens. Here, the authors show that Helicobacter pylori uses host L-lactate to generate a complement resistant state that promotes gastric colonisation.

The deciduous tree hickory (Carya cathayensis) holds economic significance in China due to its high oil content, particularly in unsaturated fatty acids. Oil bodies are crucial for storing triacylglycerol (TAG), with caleosin serving as a predominant oil body protein that aids in oil body formation and stability maintenance. Our study utilized bioinformatics techniques to identify caleosin genes within Carya cathayensis, Carya illinoinensis, and Juglans regia. Three caleosin genes were discovered in the genomes of Carya cathayensis, Carya illi-noinensis, and Juglans regia. These genes encode hydrophilic proteins. Additionally, all caleosin proteins feature a single Ca2+-binding EF-hand, a conserved “proline knot” motif, and a C-terminal hydrophilic region with four potential phosphorylation sites. The caleosin proteins in Carya cathayensis consist of α-helix, β-corner, extended chain, and random curl structures. Cis-acting elements related to stress response and hormone signaling were identified in Carya cathayensis, Carya illinoinensis, and Juglans regia, with distinct cis-acting elements implicated in seed-specific regulation in Carya cathayensis. Additionally, subcellular localization analysis confirmed that CcaCLO1 and CcaCLO2 were localized within oil bodies. Transcriptome analysis and quantitative real-time polymerase chain reaction (qRT-PCR) data demonstrated a significant up-regulation of CcaCLO1 expression during the developmental stages of the Carya cathayensis embryo. Furthermore, qPCR findings indicated that caleosins from Carya cathayensis were responsive to salt stress, with a significant up-regulation of CcaCLO1 following exposure to salt stress treatment. Consequently, caleosin genes in Carya cathayensis, Carya illinoinensis, and Juglans regia share similar physicochemical characteristics and conserved motifs. Specifically, CcaCLO1 in Carya cathayensis primarily responds to embryo development and salt stress. These findings offer foundational insights for future investigations into the regulatory mechanisms of oil accumulation and response to salt stress in hickory.

Currently, there is a pressing need to develop an agrochemical-loaded system that is both uncomplicated and efficient, thereby enhancing the adhesion of agrochemical to leaf surfaces and optimizing their insecticidal efficacy, while concurrently mitigating environmental risks. The flexible eugenol-loaded particles were synthesized via a one-step polyurethane self-assembly reaction, utilizing polyethylene glycol (PEG) as the soft segment and 4,4-diphenylmethane diisocyanate (MDI) as the hard segment. The increase in the length of the soft segment enhances the flexibility of the particles, thereby improving the contact area and adhesion with the foliar surface. When flexible particles are applied on the foliar surface, they can achieve satisfactory resistance to rainfall erosion. When the PEG molecular weight is 800, the residual concentration of eugenol can still reach 42.11% after 6 washes. The carrier protects the active ingredients and improves the resistance to ultraviolet irradiation. After 5 h of ultraviolet irradiation, the concentration of eugenol remained at 59.03% when PEG with a molecular weight of 200 was employed. Greenhouse experiments showed that the flexible transformation of particles greatly enhanced the application effect of spray on the foliar surface of particles. After undergoing three washes, the mortality of the particles can be enhanced by 5.4–8.4 times compared to that of emulsion concentrate (EC) sample. The enhancement of leaf retention performance reduces environmental risks caused by pesticide loss. Meanwhile, the controlled release of particles also reduces the acute toxicity to zebrafish. The toxicity selection pressure of the EUG@P800-Ps sample is 10.6 times that of the EC sample. In conclusion, the preparation process of the system is simple, and the flexible transformation is an effective strategy to improve the foliar application effect of spray and improve the environmental safety.

The validity of local thermodynamic equilibrium (LTE) in plasma is a long-term concern for laser-induced breakdown spectroscopy applications. In this paper, the spatial and temporal dependence of LTE deviation in picosecond laser-induced plasmas has been proved. A picosecond (∼20 ps) laser operated at 532 nm was used to ablate a silicon target to produce plasma at a pressure of 10−5 mbar. A general electron energy distribution function was used to provide access to the insight into population ratios of different energy levels for the spatially and temporally resolved optical emission intensity of laser-induced plasma. A precise temporal and spatial LTE boundary of plasma generated in picosecond laser ablation was obtained, and the results showed that only at delay times of 180–300 ns, the plasma away from the surface (>4 mm) is in LTE.

Abstract Background A subset of patients with hypertrophic cardiomyopathy (HCM) will experience adverse clinical events such as heart failure (HF), cardiovascular death, and new-onset atrial fibrillation (AF). Current risk stratification methods are imperfect and limit the identification of patients at high risk for HCM. This study aimed to evaluate the role of cardiac magnetic resonance (CMR)-derived left atrial strain parameters in the occurrence of adverse clinical events in patients with HCM. Methods Left atrial (LA) structural, functional, and strain parameters were evaluated in 99 patients with HCM and compared with 89 age-, sex-, and BMI-matched control subjects. LA strain parameters were derived from CMR two- and four-chamber cine images by a semiautomatic method. LA strain parameters include global longitudinal strain (GLS) and global circumferential strain (GCS). The LA GLS includes reservoir strain (GLS reservoir), conduit strain (GLS conduit), and booster strain (GLS booster). Three LA GLS strain rate (SR) parameters were derived: SR reservoir, SR conduit, and SR booster. The primary endpoint was set as a composite of adverse clinical events, including SCD, new-onset or worsening to hospitalized HF, new-onset AF, thromboembolic events, and fatal ventricular arrhythmias. Results LA GLS, GLS SR and GCS were impaired in HCM patients compared to control subjects (all p

Spin-orbit torques driven by the conventional spin Hall effect are widely used to switch magnetization, but this approach is nondeterministic and inefficient for magnets with perpendicular magnetic anisotropy. Here, the authors demonstrate deterministic, field-free switching in a Ni/Co multilayer by exploiting the magnetic spin Hall effect in adjacent Mn3Sn.

With the frequent occurrences of high-impact-low-probability (HILP) events such as typhoons, lightning strikes, and cyber attacks, people have the increasingly need of raising distribution network’s (DN) resilience. Deploying backup sources into the system can effectively improve the resilience of DNs. With the development of transportation electrification, the number of electric taxis (ETs) in urban transit is now growing. Besides, Vehicle-to-Grid (V2G) technology has also developed vigorously. Therefore, ETs can be dispatched to charging stations under unified command to feed power back to the grid when HILP events happen. To this end, we establish an optimization model for the post-event recovery of the DN using ETs. In this model, we combine the energy provided by V2G stations with the existing distributed generators and energy storage in the grid to restore the outage areas jointly. Topology reconfiguration technique and power flow balance of DN have also been fully considered in the modeling process. The whole grid is divided into several microgrids and powered by different sources. The multi-source multi-region power restoration method improves the stability of the DN restoration. It is easier to control the voltage and power quality. The method we proposed is tested on the modified IEEE 33-bus system. The simulation results verify the effectiveness and efficiency of our work.

Abstract Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

Abstract Radiative transfer models are widely applied in climate models to simulate vertical temperature perturbations caused by external radiative forcings. A large part of radiative transfer models is the infrared gaseous spectral transmittance scheme, which quantifies the longwave atmospheric absorption. A rapid infrared gaseous spectral transmittance scheme, called the Optimized alternate Mapping Correlated K‐Distribution model (OMCKD), is introduced in this paper. To improve the accuracy of our scheme without increasing pseudo‐monochromatic calculations, we introduce the optimal iteration method to automatically tune the equivalent absorption coefficients in the cumulative probability subspace. In addition, a new expression weighted by black‐body radiation is introduced to calculate the equivalent absorption coefficient. The OMCKD simulates heating rate and radiation flux with errors of less than 0.12 K d−1 and 0.35 W m−2, respectively, below stratopause for standard atmospheric profiles. The OMCKD is also evaluated and compared with the rapid radiative transfer model for general circulation models (RRTMG) in realistic atmospheric profiles. We found that OMCKD can accurately produce heating rates and generally captures radiative forcings associated with large perturbations to the concentrations of main greenhouse gases. Furthermore, the number of pseudo‐monochromatic calculations in OMCKD is 11.4% less than that in RRTMG, which indicates less computational cost.

IntroductionSalbutamol (SAL) is a β2 adrenergic receptor agonist which has potential hazardous effects for human health. It is very important to establish a sensitive and convenient method to monitor SAL.MethodsHere we introduce a method to combine the information from docking and site specific phage display, with the aim to obtain scFv with high affinity to SAL. First, single chain variable fragment (scFv) antibodies against SAL were generated through phage display. By using molecular docking approach, the complex structure of SAL with antibody was predicted and indicated that H3 and L3 contribute to the binding. Then new libraries were created by randomization specific residues located on H3 and L3 according to the docking results.Results and discussionAnti-SAL scFv antibodies with high efficiency were finally identified. In addition, the selected scFv was fused with alkaline phosphatase and expressed in E coli to develop a rapid and low-cost one step ELISA to detect SAL.

(1) Background: CREB-binding protein (CBP) is a key transcriptional coactivator of androgen receptors (AR). We conducted this study to investigate the effects of CBP on AR expression and proliferation in benign prostatic hyperplasia (BPH) prostate epithelial cells. (2) Methods: By analyzing a published data set, we found that CBP was closely related to the gene expression of AR in prostate cells. We enrolled 20 BPH patients who underwent transurethral resection of the prostate (TURP) in Peking University First Hospital in 2022, and analyzed the expressions of CBP and AR in BPH prostate tissues. Then, we used ICG-001 and shRNA to inhibit CBP in prostate epithelial cells (BPH-1 cells and RWPE-1 cells), and conducted immunofluorescence, cell viability assay, flow cytometry analysis, and Western blot to analyze the effects of CBP on AR expression and proliferation in prostate epithelial cells. We also studied the interaction between CBP and AR through a co-immunoprecipitation assay. (3) Results: CBP is consistent with AR in expression intensity in prostate tissues. Inhibiting CBP decreases AR expression, and induces proliferation inhibition, apoptosis, and cell cycle arrest in BPH prostate epithelial cells. The co-immunoprecipitation assay showed that CBP binds with AR to form transcription complexes in prostate epithelial cells. (4) Conclusions: Inhibiting CBP decreases AR expression and inhibits proliferation in benign prostate epithelial cells. CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH.

MIKC-type MADS-box genes, also known as type II genes, play a crucial role in regulating the formation of floral organs and reproductive development in plants. However, the genome-wide identification and characterization of type II genes as well as a transcriptomic survey of their potential roles in Carica papaya remain unresolved. Here, we identified and characterized 24 type II genes in the C. papaya genome, and investigated their evolutional scenario and potential roles with a widespread expression profile. The type II genes were divided into thirteen subclades, and gene loss events likely occurred in papaya, as evidenced by the contracted member size of most subclades. Gene duplication mainly contributed to MIKC-type gene formation in papaya, and the duplicated gene pairs displayed prevalent expression divergence, implying the evolutionary significance of gene duplication in shaping the diversity of type II genes in papaya. A large-scale transcriptome analysis of 152 samples indicated that different subclasses of these genes showed distinct expression patterns in various tissues, biotic stress response, and abiotic stress response, reflecting their divergent functions. The hub-network of male and female flowers and qRT-PCR suggested that TT16-3 and AGL8 participated in male flower development and seed germination. Overall, this study provides valuable insights into the evolution and functions of MIKC-type genes in C. papaya.

The synthesis of upconversion nanoparticles (UCNPs) by flame aerosol is of great significance to realize industrial large-scale production of UCNPs and develop nanotechnology further. Here, for the first time, we successfully fabricated the ultrasmall Y2O3:Yb3+/Ho3+ UCNPs by a self-build swirl flame spray pyrolysis (SFSP) method with a high production rate of ∼40 g$ \cdot $ h−1. These flame-made UCNPs are all pure cubic phases with an average ultrasmall size of ∼14 nm. Excited by 980 nm laser, the synthesized UCNPs show bright green (2F4, 5S2 → 5I8) and relatively weak red (5F5 → 5I8) upconversion luminescence (UCL). Based on the UCL spectra of Y2O3:Yb3+/Ho3+ UCNPs, the optimal doping concentrations of 6 mol% Yb3+ and 0.1 mol% Ho3+ were determined to reach the most intense UCL. The dependence of UCL intensity and pump power was further analyzed, and it indicated that the green and red UCL are two-photon processes. In addition, the UCL properties with different synthesized conditions were also demonstrated. The UCL mechanism of these flame-made Y2O3:Yb3+/Ho3+ UCNPs were illustrated in detail. Our results prove that industrial large-scale production of continuous one-step synthesis of UCNPs by flame aerosol technology is completely feasible and deserves further study.

Coffee pulp is an underutilized by-product of coffee industrial production rich in bioactive compounds such as phenolic compounds, caffeine, and dietary fiber. The widely known antioxidant, anti-inflammatory, anti-aging, antimicrobial and hepatoprotective health-promoting properties attributed to mentioned compounds enhance the use of coffee pulp as a bioactive food ingredient. Furthermore, the application of green sustainable extraction techniques pursuing highly efficient and selective extraction processes promotes this by-product exploitation in food science. Hence, this review gathers the available information relative to the impact of the extraction processes on the bioactive compound's recovery from coffee pulp, providing an overview of the most recent advances. An in-depth comparison workout between conventional and alternative extraction methods was performed to identify the most suitable techniques for coffee pulp valorization as functional ingredient until date. A critical discussion focused on advantages and drawbacks of the extraction methods applied to coffee pulp was included together a prospective of emerging extraction techniques.

Indian Ocean dipole (IOD) is one of the dominant modes of interannual variability in the Indian Ocean, which has global climate impacts and thus is one of the key targets of seasonal predictions. In this study, based on a century-long seasonal hindcast experiment from the Coupled Seasonal Forecasts of the 20th century (CSF-20C), we show that the prediction skill for IOD exhibits remarkable decadal variations, with low skill in the early-to-mid 20th century but high skill in the second half of the 20th century. The decadal variations of prediction skills for IOD are caused by two factors. The first is associated with the decadal variation of the ENSO-IOD relationship. Although individual members of the predictions can simulate the variation of the ENSO-IOD relationship, with amplitude close to that in the observation, the feature is greatly suppressed in the ensemble mean due to the asynchrony of variation phases among individual members. In the ensemble mean, the IOD evolution shows an unrealistic stable and high correlation with ENSO evolution. This causes the prediction to have much higher skill for those periods during which IOD is accompanied by ENSO in the observation. The second factor is associated with the decadal variation of IOD predictability in the prediction system. In the prediction system, the decadal variation of IOD signal strength closely follows that of ENSO signal strength. Meanwhile, the IOD noise strength shows variations opposite to the IOD signal strength. As a result, the signal-to-noise ratio greatly increases in the second half of the 20th century due to the enhancement of the ENSO signal strength, which represents the increase of IOD predictability in the prediction system.

Tidal asymmetry is one of the main factors for generating net transport for waterborne materials in tidal estuaries, and thus, this phenomenon has significant influences on controlling morphological development and the ecological environment. Tidal propagation is sensitive to changes in the coastline and geometry of estuarine regions. Moreover, tidal waveforms vary with various factors, such as coastline changes and bathymetry evolution due to local anthropogenic activities. The topography of Lingding Bay (LDB) of the Pearl River Estuary (PRE) has greatly changed since the 1960s because of human interventions, but the response of tidal duration asymmetry (TDA) to morphological changes is still poorly understood. Utilizing the two-dimensional Delft-3D flexible mesh numerical model, the spatial pattern of TDA and its primary contributors in LDB of the PRE were reproduced for 1964, 1989, and 2016, accounting for the changes in both shoreline and bathymetry owing to human interventions. The results reveal that as the tidal wave propagates upstream, the tidal skewness increases from negative values to positive values longitudinally, indicating the transition from a shorter ebb-duration state to a shorter flood-duration state. Additionally, a prominent shift in TDA and its primary contributors takes place approximately in the period of 1989. In 1964-1989, the tidal skewness increased by at least 0.1 throughout the LDB, indicating that the flood duration of the entire bay was shortened significantly. However, in 1989-2016, the tidal skewness decreased by at most 0.15 throughout the LDB, representing a longer flood duration in the entire LDB. The scenario simulations reveal that reclamation-induced shoreline changes control the increase in TDA and its primary contributors by enhancing width convergence of estuary in the period of 1964-1989. Conversely, the increase in water depth plays a vital role in the decrease of TDA in the period of 1989-2016. The results obtained from this study are particularly useful for understanding the controlled factors contributing to net sediment transport and the associated long-term morphological evolution in estuaries heavily impacted by human interventions.

Microneedle puncture is a standard minimally invasive treatment and surgical method, which is widely used in extracting blood, tissues, and their secretions for pathological examination, needle-puncture-directed drug therapy, local anaesthesia, microwave ablation needle therapy, radiotherapy, and other procedures. The use of robots for microneedle puncture has become a worldwide research hotspot, and medical imaging navigation technology plays an essential role in preoperative robotic puncture path planning, intraoperative assisted puncture, and surgical efficacy detection. This paper introduces medical imaging technology and minimally invasive puncture robots, reviews the current status of research on the application of medical imaging navigation technology in minimally invasive puncture robots, and points out its future development trends and challenges.

Helicobacter pylori is a gastric pathogen that infects nearly half of the global population and is recognized as a group 1 carcinogen by the Word Health Organization. The global rise in antibiotic resistance has increased clinical challenges in treating H. pylori infections. Biofilm growth has been proposed to contribute to H. pylori’s chronic colonization of the host stomach, treatment failures, and the eventual development of gastric diseases. Several components of H. pylori have been identified to promote biofilm growth, and several of these may also facilitate antibiotic tolerance, including the extracellular matrix, outer membrane proteins, shifted morphology, modulated metabolism, efflux pumps, and virulence factors. Recent developments in therapeutic approaches targeting H. pylori biofilm have shown that synthetic compounds, such as small molecule drugs and plant-derived compounds, are effective at eradicating H. pylori biofilms. These combined topics highlight the necessity for biofilm-based research in H. pylori, to improve current H. pylori-targeted therapeutic approaches and alleviate relative public health burden. In this review we discuss recent discoveries that have decoded the life cycle of H. pylori biofilms and current biofilm-targeted treatment strategies.

Infrared and visible image fusion aims to preserve essential thermal information and crucial visible details from two types of input images to generate an informative fusion image for better visual perception. In recent years, several hybrid methods have been applied in the field of infrared and visible image fusion. In this paper, we proposed a novel image fusion method based on particle swarm optimization and dense block for visible and infrared images. Particle swarm optimization is utilized to optimize the weighting factors of the coefficients obtained by discrete wavelet transform, then the coefficients are fused with the optimum weight to obtain the initial fusion image. The final fusion image is created by integrating the first fused image with the input visible image using a deep learning model, in which dense block is utilized for better feature extraction ability. The results of comparison experiments demonstrate that our method produces fusion images with richer details and texture features, and the fused image reduces the artifacts and noise.

Temperature and humidity profiles in the atmospheric boundary layer are essential for climate studies. The ground-based infrared hyperspectral spectrometer has the advantage of measuring radiances emitted from the atmosphere at a high temporal and moderate vertical resolution. In this article, the retrieval of temperature and humidity profiles from ground-based infrared hyperspectral observations is exploited. Although existing inversion algorithms based on physical models or statistical learning have made some progress, they still suffer from high computational complexity or poor performance. Motivated by the strength of the deep learning, we present a deep retrieval architecture (DReA) by skillfully designing a light-weight one-dimensional convolution neural network (CNN) to retrieve the temperature and humidity profiles. Experiments were conducted using atmospheric emitted radiance interferometer (AERI) and radiosonde data to demonstrate the superiority of the proposed DReA. The validation of the DReA with the radiosonde, using 802 profiles with 37 layers below 3 km, presents an excellent retrieval ability with a root mean square error (RMSE) of 0.87 K for the temperature and 1.06 g/kg for the water vapor mixing ratio. Furthermore, a thorough comparison with commonly used inversion methods such as the traditional back propagation (BP) and the eigenvector (EV) regression method, shows that our proposed DReA method obtains a leading solution in retrieving temperature and humidity profiles.

BackgroundAntibody–drug conjugates (ADC), such as enfortumab vedotin (EV), sacituzumab govitecan (SG), and RC-48, have shown outstanding response rates to local advanced or metastatic urothelial carcinoma (UC). However, their corresponding target expression characteristics in UC and its histologic variants were unknown.MethodsWe detected the expression of NECTIN-4, TROP-2, and HER2, which are the corresponding targets of ADCs EV, SG, and RC-48 in muscle-invasive UC through immunohistochemistry.Results161 consecutive samples from 2017 to 2021 of muscle-invasive UC and its histologic variants were obtained in Peking University First Hospital. Variant histology types included 72UC, 10 squamous carcinomas, 23 glandular carcinomas, 19 small cell carcinomas, 19 micropapillary variants, and 18 nested variants. NECTIN-4 expression was found to be 57/72 (79.2%), 10/10 (100%), 15/23 (65.2%), 4/19 (21.1%), 15/19 (78.9%), and 16/18 (88.9%) in conventional UC, squamous carcinoma, glandular carcinoma, small cell carcinoma, micropapillary, and nested variant, respectively, compared with 65/72 (90.3%), 8/10 (80.0%), 13/23 (56.5%), 3/19 (15.8%), 16/19 (84.2%), and 15/18 (83.3%) of TROP-2, and 26/72 (36.1%), 0, 5/23 (21.7%), 6/19 (31.6%), 5/19 (26.3%), and 7/18 (38.9%) of HER2.

The prediction of the estrogen receptor (ER) and androgen receptor (AR) activity of a compound is quite important to avoid the environmental exposures of endocrine-disrupting chemicals. The Estrogen and Androgen Receptor Database (EARDB, http://eardb.schanglab.org.cn/) provides a unique collection of reported ERα, ERβ, or AR protein structures and known small molecule modulators. With the user-uploaded query molecules, molecular docking based on multi-conformations of a single target will be performed. Moreover, the 2D similarity search against known modulators is also provided. Molecules predicted with a low binding energy or high similarity to known ERα, ERβ, or AR modulators may be potential endocrine-disrupting chemicals or new modulators. The server provides a tool to predict the endocrine activity for compounds of interests, benefiting for the ER and AR drug design and endocrine-disrupting chemical identification.

Oil recovery is an essential parameter for reservoir development performance evaluation, but there is no specific research on the theoretical oil recovery prediction model of polymer microspheres (PMs)’ conformance control. This research aims to establish an oil recovery prediction model that depends on the definition of oil recovery based on stream tube theory. PMs’ enhanced oil recovery mechanism is to plug the pore throat to expand the swept area. The assumption that the stream tube between injection and production wells is trapezoidal is proposed. Based on this premise, the area sweep efficiency equation suitable for the rhombus inverse nine-spot well pattern is established based on the stream tube theory. The vertical sweep efficiency equation is optimized by introducing the equivalent mobility ratio. Additionally, the model’s adaptability and validity are studied. The analysis results show that oil recovery decreases with increasing injection rate, injection concentration, and PMs size but increases with the increasing injection period. The theoretical oil recovery is 1.37%, and the actual oil recovery of the field application is 1.22%, with an error of 0.15%. This model has good consistency with the actual physical process of the field application. The oil recovery prediction model can provide oil recovery and optimize PMs’ conformance control injection scheme. This study fills the gap in the mathematical model for oil recovery prediction of PMs’ conformance control.

The application of wearable devices for fall detection has been the focus of much research over the past few years. One of the most common problems in established fall detection systems is the large number of false positives in the recognition schemes. In this paper, to make full use of the dependence between human joints and improve the accuracy and reliability of fall detection, a fall-recognition method based on the skeleton and spatial-temporal graph convolutional networks (ST-GCN) was proposed, using the human motion data of body joints acquired by inertial measurement units (IMUs). Firstly, the motion data of five inertial sensors were extracted from the UP-Fall dataset and a human skeleton model for fall detection was established through the natural connection relationship of body joints; after that, the ST-GCN-based fall-detection model was established to extract the motion features of human falls and the activities of daily living (ADLs) at the spatial and temporal scales for fall detection; then, the influence of two hyperparameters and window size on the algorithm performance was discussed; finally, the recognition results of ST-GCN were also compared with those of MLP, CNN, RNN, LSTM, TCN, TST, and MiniRocket. The experimental results showed that the ST-GCN fall-detection model outperformed the other seven algorithms in terms of accuracy, precision, recall, and F1-score. This study provides a new method for IMU-based fall detection, which has the reference significance for improving the accuracy and robustness of fall detection.

BackgroundIncreasing researches have been reported that epigenetic alterations play critical roles in ESCC development. However, the role of the histone demethylase KDM4D in ESCC tumorigenesis is poorly investigated. This study aims to discover the underlying mechanisms between KDM4D and ESCC progression.MethodsCCK-8 assays, clone formation assay and soft-agar assays were performed to assess cell proliferation. Transwell assay was utilized to assess cell migration efficiency, while sphere formation assay was used to evaluate the cell self-renewal ability. Bioinformatic analysis was conducted to identify prognostic factors and predict the potential E3 ubiquitin ligases. In vitro ubiquitination assay was conducted to confirm the regulations between SYVN1 and HMGB1. The mRNA levels or protein levels of genes were detected by real-time PCR and western blot analysis. In vivo tumor xenograft models were used to determine whether the HMGB1 inhibition affected the malignant features of ESCC cells.ResultEpigenome screening and low-throughput validations highlighted that KDM4D is a tumor suppressor in ESCC. KDM4D expressed lowly in tumors that predicts poor prognosis. KDM4D deficiency significantly enhanced tumor growth, migration and stemness. Mechanistically, KDM4D transcriptionally activates SYVN1 expressions via H3K9me3 demethylation at the promoter region, thereby triggering the ubiquitin-dependent degradation of HMGB1. Low KDM4D depended on accumulated HMGB1 to drive ESCC progression and aggressiveness. Targeting HMGB1 (Glycyrrhizin) could remarkably suppress ESCC tumor growth in vitro and in vivo, especially in KDM4D-deficient cells.ConclusionsWe systematically identified KDM4D/SYVN1/HMGB1 axis in ESCC progression, proving novel biomarkers and potential therapeutic targets.

Background and objectives: Objective, accurate, and intuitive evaluation of knee joint function in patients with knee osteoarthritis (KOA) is important. This study aimed to clarify the gait characteristics of patients with bilateral KOA and their correlation with Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Materials and Methods: 20 patients with bilateral KOA and 20 conditionally matched healthy individuals were enrolled in the experimental and control groups, respectively. Footscan and CODA motion gait analysis systems were used to analyse the gait parameters. Gait spatiotemporal parameters and knee joint motion parameters were collected. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Patients in the experimental group were evaluated using WOMAC. Pearson’s correlation analysis was performed on the gait data and WOMAC score data of the experimental group. Results: Velocity, cadence, step length, and stride length of the experimental group were significantly lower than those of the control group (p < 0.01). Step time and gait cycle were significantly greater in the experimental group than in the control group (p < 0.01). Total stance and double-stance times of the experimental group were significantly greater than those of the control group (p < 0.01), whereas the single-stance time was shorter than that of the control group (p < 0.01). The range of motion and maximum flexion angle in the experimental group were significantly lower than those in the control group (p < 0.01), and the minimum angle of knee extension was greater than that in the control group (p < 0.01). The discrete trend of weight-bearing balance and walking stability gait index in the experimental group was greater than that in the control group. The WOMAC score and gait analysis were significantly correlated (p < 0.05). Conclusions: The gait function of patients with KOA is significantly worse than that of normal people. The WOMAC scale and gait analysis can be used to assess KOA severity from different perspectives with good consistency.

The Mu Us Sandy Land is a key region of man-made desert control and farmland to forest (grass) return in China. Despite global change and the strong influence of human activities, the vegetation in this region has been significantly improved and restored. In this study, multisource remote sensing data and multiple indicators were used to quantitatively monitor and evaluate the vegetation restoration status in this area. The driving factors were also analysed. The results show that in the past 20 years, nearly the entire Mu Us Sandy Land significantly and substantively recovered. The regional fractional vegetation cover increased, with an average annual growth rate of 0.59% and obvious spatial heterogeneity. The nine most important driving factors could comprehensively account for 58.38% of the spatial distribution of the vegetation coverage. Factors such as land use and land cover, the aridity index, and gross domestic product had the most significant impact, followed by precipitation and temperature. The results confirmed that the vegetation was restored and improved in the Mu Us Sandy Land and determined the main driving factors, which is helpful for vegetation restoration and ecological improvement on sandy land similar to the Mu Us Sandy Land.

The invariant imbedding T-matrix (IIM T-matrix) model is regarded as one of the most promising models for calculating the scattering parameters of non-spherical particles. However, the IIM T-matrix model needs to be iterated along the radial direction when calculating the T-matrix, which involves complex calculations such as matrix inversion and multiplication. Therefore, how to improve its computational efficiency is an important problem to be solved. Focused on particles with N-fold symmetric geometry, this paper deduced the symmetry in the calculation process of the IIM T-matrix model, derived the block iteration scheme of the T-matrix, and contracted the IIM T-matrix program for particles with N-fold symmetric geometry. Discrete Dipole Approximation (DDA) and Geometrical Optics Approximation (IGOA) were employed to verify the accuracy of the improved IIM T-matrix model. The results show that the six phase matrix elements (P11, P12/P11, P22/P11, P33/P11, P34/P11 and P44/P11) calculated by our model are in good agreement with other models. The computational efficiency of the improved IIM T-matrix model was further investigated. As demonstrated by the results, the computational efficiency for the particles with N-fold symmetry improved by nearly 70% with the improvement of the symmetry of U matrix and T matrix. In conclusion, the improved model can remarkably reduce the calculation time while maintaining high accuracy.

Celiac disease (CD) is an autoimmune intestinal disorder caused by the ingestion of gluten in people who carry the susceptible gene. In current celiac disease research, wheat gluten is often the main target of attention, neglecting the role played by non-gluten proteins. This study aimed to describe the effects of wheat amylase trypsin inhibitors (ATI, non-gluten proteins) and gliadin in BALB/c mice while exploring the further role of relevant adjuvants (cholera toxin, polyinosinic: polycytidylic acid and dextran sulfate sodium) intervention. An ex vivo splenocyte and intestinal tissue were collected for analysis of the inflammatory profile. The consumption of gliadin and ATI caused intestinal inflammation in mice. Moreover, the histopathology staining of four intestinal sections (duodenum, jejunum, terminal ileum, and middle colon) indicated that adjuvants, especially polyinosinic: polycytidylic acid, enhanced the villi damage and crypt hyperplasia in co-stimulation with ATI and gliadin murine model. Immunohistochemical results showed that tissue transglutaminase and IL-15 expression were significantly increased in the jejunal tissue of mice treated with ATI and gliadin. Similarly, the expression of inflammatory factors (TNF-α, IL-1β, IL-4, IL-13) and Th1/Th2 balance also showed that the inflammation response was significantly increased after co-stimulation with ATI and gliadin. This study provided new evidence for the role of wheat amylase trypsin inhibitors in the pathogenesis of celiac disease.

Infrared hyperspectral remote sensing has been widely used in the field of meteorology. Many scientists have carried out research on inversion methods of meteorological elements such as thermodynamic profile, boundary layer height, cloud base height, etc. In this study, a method based on machine learning for cloud detection using ground-based infrared hyperspectral radiation data is proposed. The features of outliers, the cloudy and cloud-free data of Atmospheric Emitted Radiance Interferometer (AERI) radiation are extracted. The “reference values” of cloudy and cloud-free are determined based on the observation data of Vaisala CL31 ceilometer within the time range of 8 min before the corresponding time of AERI. A support vector machine (SVM) algorithm is used for training. The dataset comes from the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site and North Slope Alaska (NSA) site from 2015 to 2017, and the ARM West Antarctic Radiation Experiment (AWARE) site in 2016 is also analyzed. The instruments used in this paper include AERI, ceilometer, etc. The experimental results reveal that the agreement of cloud detection results between the proposed algorithm and ceilometer is about 93% at each site. However, for high clouds or optically thin clouds, the agreement will decrease.

The frequent and massive use of chlorfenapyr has led to pesticide residues in crops, threatening food safety and human health. However, there is limited research on the detection of tralopyril, which is the major metabolite of chlorfenapyr with high toxicity. This study aimed to develop a novel, sensitive, and highly efficient method for the determination of chlorfenapyr and tralopyril residues in 16 crops. The optimized purification procedure provided satisfactory recovery of 76.6–110%, with relative standard deviations of 1.3–11.1%. The quantification values of pesticides in crop matrixes were all 0.01 μg kg−1. The optimal method was adopted to determine the chlorfenapyr and tralopyril residues in field trials in 12 regions in China and monitor their residues in 16 agricultural products. The results of the dissipation and terminal residue experiments show that the final residue of chlorfenapyr was less than MRL (maximum residue limit) and no tralopyril was detected in the field samples. Moreover, the qualification proportion of these residues in market samples were up to 99.5%. The RQ (risk quotient) values of chlorfenapyr and chlorfenapyr with consideration of tralopyril were both apparently lower than an RQ of 100%, indicating an acceptable level. This research provides a thorough long-term dietary risk evaluation on chlorfenapyr and tralopyril and would provide reference for their scientific and safe utilization.