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Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Abstract Background The aims of this study were to evaluate the levels of preretinal oxygen tension in patients with diabetes who did not have hypertension by using three-dimensional spoiled gradient-recalled (3D-SPGR) echo sequence imaging and to explore the correlation between diabetic retinopathy (DR) and changes in preretinal oxygen tension. Method This study involved 15 patients with type 2 diabetes without hypertension, who were divided into a diabetic retinopathy (DR) group (n = 10 eyes) and a diabetic non-retinopathy (NDR) group (n = 20 eyes), according to the results of a fundus photography test. Another healthy control group (n = 14 eyes) also participated in the study. The preretinal vitreous optic disc area, nasal side, and temporal side signal intensity of the eyes was assessed before and after oxygen inhalation with the use of 3D-SPGR echo magnetic resonance imaging (MRI). The signal acquisition time was 10, 20, 30, 40, and 50 min after oxygen inhalation. Results The results showed that, in the DR and NDR groups, the preretinal vitreous oxygen tension increased rapidly at 10 min after oxygen inhalation and peaked at 30–40 min, and the increased slope of the DR group was higher than that of the NDR group. The oxygen tension of the preretinal vitreous gradually increased after oxygen inhalation, and the difference between the DR and NDR groups and the control group was statistically significant (P

Diagnosis of gastric cancer currently requires gastroscopic biopsy, which requires time and expertize to perform. Here, the authors demonstrate a femto-SRS imaging method which showed high accuracy in diagnosing gastric cancer without the need for pathologistbased diagnosis.

PurposeImmune checkpoint blockade (ICB) therapy has transformed the treatment of triple-negative breast cancer (TNBC) in recent years. However, some TNBC patients with high programmed death-ligand 1 (PD-L1) expression levels develop immune checkpoint resistance. Hence, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to construct prognostic models of patient survival outcomes in order to understand biological mechanisms operating within the tumor microenvironment.Patients and methodsRNA sequence (RNA-seq) data from 303 TNBC samples were analyzed using an unsupervised cluster analysis approach to reveal distinctive cellular gene expression patterns within the TNBC tumor microenvironment (TME). A panel of T cell exhaustion signatures, immunosuppressive cell subtypes and clinical features were correlated with the immunotherapeutic response, as assessed according to gene expression patterns. The test dataset was then used to confirm the occurrence of immune depletion status and prognostic features and to formulate clinical treatment recommendations. Concurrently, a reliable risk prediction model and clinical treatment strategy were proposed based on TME immunosuppressive signature differences between TNBC patients with good versus poor survival status and other clinical prognostic factors.ResultsSignificantly enriched TNBC microenvironment T cell depletion signatures were detected in the analyzed RNA-seq data. A high proportion of certain immunosuppressive cell subtypes, 9 inhibitory checkpoints and enhanced anti-inflammatory cytokine expression profiles were noted in 21.4% of TNBC patients that led to the designation of this group of immunosuppressed patients as the immune depletion class (IDC). Although IDC group TNBC samples contained tumor-infiltrating lymphocytes present at high densities, IDC patient prognosis was poor. Notably, PD-L1 expression was relatively elevated in IDC patients that indicated their cancers were resistant to ICB treatment. Based on these findings, a set of gene expression signatures predicting IDC group PD-L1 resistance was identified then used to develop risk models for use in predicting clinical therapeutic outcomes.ConclusionA novel TNBC immunosuppressive tumor microenvironment subtype associated with strong PD-L1 expression and possible resistance to ICB treatment was identified. This comprehensive gene expression pattern may provide fresh insights into drug resistance mechanisms for use in optimizing immunotherapeutic approaches for TNBC patients.

BackgroundNeck pain is a prevalent condition that causes an enormous health care burden due to the lack of efficient therapies. As a promising technology, virtual reality (VR) has shown advantages in orthopedic rehabilitation. However, there is no meta-analysis evaluating the effectiveness of VR in neck pain management. ObjectiveThis study aims to review original randomized controlled trials (RCTs) evaluating the effectiveness of VR for neck pain and to provide evidence for the clinical application of a new alternative approach for pain management. MethodsA total of 9 electronic databases were systematically searched for relevant articles published from inception to October 2022. RCTs in English or Chinese that investigated VR therapy for participants with neck pain were included. The methodological quality and the evidence level were assessed using the Cochrane Back and Neck Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline, respectively. ResultsA total of 8 studies with 382 participants were included for the final analysis. For the pain intensity, the overall pooled effect size was 0.51, with a standardized mean difference (SMD) of −0.51 (95% CI −0.91 to −0.11; GRADE: moderate), favoring VR therapy compared with controls. Subgroups analyses revealed that significant differences in pain intensity were found in the multimodal intervention (VR in combination with other therapies) than in other interventions (SMD −0.45, 95% CI −0.78 to −0.13; GRADE: moderate), and better analgesic effects were also observed in patients with chronic neck pain receiving VR intervention (SMD −0.70, 95% CI −1.08 to −0.32; GRADE: moderate) and patients treated in the clinic or research unit (SMD −0.52, 95% CI −0.99 to −0.05; GRADE: moderate) than controls. Regarding other health outcomes, the VR experienced less disability, lower kinesiophobia, and greater kinematic function (cervical range of motion, mean and peak velocity). Nevertheless, the follow-up effects of VR therapy on pain intensity and disability were not found. ConclusionsExisting moderate evidence support VR as a beneficial nonpharmacological approach to improve pain intensity in patients with neck pain, with advantages to multimodal intervention, people with chronic neck pain, and clinic or research unit–based VR therapy. However, the limited quantity and high heterogeneity of the articles limit our findings. Trial RegistrationPROSPERO CRD42020188635; https://tinyurl.com/2839jh8w

Heart failure is a complex chronic condition that results in multiple patient visits throughout the care continuum. Patient experience has associations with clinical outcomes. The purpose of this study was to examine patient experience among the underserved in a specialized interprofessional collaborative practice heart failure clinic. This prospective study utilized both qualitative and quantitative data to describe the patient experience within an interprofessional collaborative practice. Data were collected from patient experience surveys in 1128 patients seen in the Heart Failure Transitional Care Services for Adults (HRTSA) clinic between January 1, 2018, and December 31, 2021. Interprofessional collaborative practice surveys were completed by clinic staff members. When examining relationships associated with patient experience, we found three significant associations. Being single was negatively associated with patient experience. When examining IPCP and patient experience, overall interprofessional collaborative practice alignment [t(237)=2.00, p=.046 ] and the team’s alignment of mission, vision and purpose [t(254)=1.99, p=.047] were positively related to patients’ care satisfaction. Interprofessional collaborative practice team alignment can positively impact patient experience in underserved patients with heart failure. Experience Framework This article is associated with the Quality & Clinical Excellence lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens.

Although the physicochemical properties of gallium selenide (GaSe) have been widely investigated, the property and application exploration of GaSe‐coupled fiber devices are still in its infancy. There are obvious challenges, namely, selecting from multiple GaSe phases and effectively coupling to the unique fiber structure. Herein, lab‐on‐fiber (LOF) based on optimized GaSe is proposed to be used for robust femtosecond pulse generation and fiber‐compatible photodetection. First, based on density functional theory (DFT) calculations, ε‐GaSe is selected as a preferable model material for its suitable band structures, low work function, and high damage threshold. Benefiting from the fiber‐compatible ε‐GaSe combined with micro–nano processing, stable femtosecond soliton pulse (≈303 fs, 16.67 MHz, 51.64 dB) output and multiwavelength (520, 808, and 1550 nm) detection are realized in LOF. These results pave the way for optics research of polyphase semiconductors and design of integrated all‐fiber devices.

BackgroundStress hyperglycemia ratio (SHR) was developed to reduce the impact of long-term chronic glycemic factors on stress hyperglycemia levels, which have been linked to clinical adverse events. However, the relationship between SHR and the short- and long-term prognoses of intensive care unit (ICU) patients remains unclear.MethodsWe retrospectively analyzed 3,887 ICU patients (cohort 1) whose initial fasting blood glucose and hemoglobin A1c data within 24 hours of admission were available and 3,636 ICU patients (cohort 2) who were followed-up for 1-year using the Medical Information Mart for Intensive Care IV v2.0 database. Patients were divided into two groups based on the optimal cutoff value of SHR, which was determined using the receiver operating characteristic (ROC) curve.ResultsThere were 176 ICU deaths in cohort 1 and 378 patients experienced all-cause mortality during 1 year of follow-up in cohort 2. The results of logistic regression revealed that SHR was associated with ICU death (odds ratio 2.92 [95% confidence interval 2.14–3.97] P < 0.001), and non-diabetic patients rather than diabetic patients showed an increased risk of ICU death. As per the Cox proportional hazards model, the high SHR group experienced a higher incidence of 1-year all-cause mortality (hazard ratio 1.55 [95% confidence interval 1.26–1.90] P < 0.001). Moreover, SHR had an incremental effect on various illness scores in predicting ICU all-cause mortality.ConclusionSHR is linked to ICU death and 1-year all-cause mortality in critically ill patients, and it has an incremental predictive value in different illness scores. Moreover, we found that non-diabetic patients, rather than diabetic patients, showed an increased risk of all-cause mortality.

Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and α-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.

Due to construction industry projects’ large-scale, long-period, and outdoor operation characteristics, employees’ organizational citizenship behavior (OCB) plays an essential role in cost-saving, high-efficiency, and environmentally friendly development strategies. This study discusses how to improve employees’ OCB from two levels of employees’ psychological factors and corporate social responsibility (CSR) at the organizational level. We verified this study’s hypotheses based on 336 valid questionnaires collected from 56 teams. The results indicated that (1) positive psychological capital (PsyCap) was a positive predictor of employees’ OCB; (2) PsyCap was positively related to employees’ prosocial motivation, and prosocial motivation partially mediated the relationship between PsyCap and employees’ OCB; and (3) CSR moderated the relationship between PsyCap and prosocial motivation and played a significant moderating role between prosocial motivation and OCB. These findings provide an empirical research basis for the theories of conservation of resources (COR), self-determination, and affective events. This research also has managerial implications for improving employees’ OCB in the construction industry.

Existing transmission lines and pipelines are frequently crossed and erected in parallel, meaning that if lightning strikes a wire and causes insulator flashovers, the resulting lightning current will spread through the grounding of the tower where the flashover insulator is located. This dispersion of current can lead to overvoltage effects on nearby pipelines. This study performs simulation calculations to analyze the overvoltage experienced by pipelines due to the dispersion of grounding current from the tower. Furthermore, this paper proposes a method for protecting the pipeline from such an overvoltage. Firstly, the lightning transient calculation model of a transmission line tower is constructed using the electromagnetic transient software ATP-EMTP 5.5. The model calculates the effects of lightning peak currents and soil resistivity on the distribution characteristics of lightning current in the tower, specifically in the area where the flashover insulator is located. Subsequently, a calculation model of the tower grounding grid–natural gas pipeline is developed, taking into account the distribution characteristics of lightning current in the tower. This model analyzes the impact of lightning peak currents, soil resistivity, and pipeline spacing on pipeline overvoltage. Finally, the effectiveness of the solid-state decoupler in mitigating lightning overvoltage in the pipeline is verified. The results demonstrate a positive correlation between the lightning current entering the tower grounding grid through the flashover insulator and the lightning current distribution characteristics. The solid-state decoupling device proves to be effective in reducing the voltage of the pipeline insulation layer, and the simulation results provide the optimal laying length of the bare copper wire.

Estimating the complete 3D points of crop plants from incomplete points is vital for phenotyping and smart agriculture management. Compared with the completion of regular man-made objects such as airplanes, chairs, and desks, the completion of corn plant points is more difficult for thin, curled, and irregular corn leaves. This study focuses on MSGRNet+OA, which is based on GRNet, to complete a 3D point cloud of thin corn plants. The developed MSGRNet+OA was accompanied by gridding, multi-scale 3DCNN, gridding reverse, cubic feature sampling, and offset-attention. In this paper, we propose the introduction of a 3D grid as an intermediate representation to regularize the unorganized point cloud, use multi-scale predictive fusion to utilize global information at different scales, and model the geometric features by adding offset-attention to compute the point position offsets. These techniques enable the network to exhibit good adaptability and robustness in dealing with irregular and varying point cloud structures. The accuracy assessment results show that the accuracy of completion using MSGRNet+OA is superlative, with a CD (×10−4) of 1.258 and an F-Score@1% of 0.843. MSGRNet+OA is the most effective when compared with other networks (PCN, shape inversion, the original GRNet, SeedFormer, and PMP-Net++), and it improves the accuracy of the CD (×10−4)/F-Score@1% with −15.882/0.404, −15.96/0.450, −0.181/0.018, −1.852/0.274, and −1.471/0.203, respectively. These results reveal that the developed MSGRNet+OA can be used to complete a 3D point cloud of thin corn leaves for phenotyping.

Rapid economic growth puts the natural environment under tremendous pressure. As a traditional chemical company, it is important to reconsider outdated business development models, develop innovative green initiatives for long-term growth, and choose approaches to address environmental issues. Determining how to encourage employees’ green performance while balancing environmental issues is crucial for chemical companies in the current social and economic environment. This study investigates the green transformational leadership style to enhance green performance of chemical company employees. It expands the field of environmental protection by employing two novel constructs: creative process engagement and green creativity. We collected 623 valid questionnaires from 98 teams (98 leaders and 525 employees) and used SPSS 26.0, HLM 6.0, and MPlus 8.3 to test the hypothesis. The findings revealed that (1) green transformational leadership positively influences individual green performance, (2) creative process engagement and green creativity mediate the relationship between green transformational leadership and individual green performance, and (3) individual environmental awareness positively moderates the relationship between green transformational leadership and green creativity. These novel findings contribute to the environmental literature and help chemical company managers in enhancing employee innovation and performance.

In this paper, we analyze the residual stress of different components of the crystal structures of electronic device materials following exposure to elevated temperatures using a combination of experimental tests and finite element simulations. X-ray diffraction (XRD) and LXRD micro-area residual stress analyzer were employed to determine the residual strain and stress of the CBGA sample encapsulation cover and solder joints. Subsequently, the experimental data were utilized to verify the accuracy of the simulation. The discrepancy between experimental measurements and simulation outcomes of the residual stress following reflow soldering of CBGA-assembled micro-solder joints is below 14%. The analysis also included thermal warping deformation of the CBGA encapsulation cover and how the residual stress was influenced by the diameter, spacing, and height of the solder joints. The study reveals that the residual stress following reflow soldering of BGA solder joints is non-uniformly distributed within the array. Within a single solder joint, residual stress gradually increases in distribution from its middle to the point where it make contact with the PCB and chip, with the highest level of residual stress observed where the solder joint contacts the chip. The variation in material parameters, such as the coefficient of thermal expansion, is the primary cause of thermal warping deformation on the surface of CBGA encapsulation covers. Three primary factors significantly impact the residual stress on BGA solder joints: solder joint diameter, spacing, and height. The maximum value is inversely proportional to the height of the solder joints and the residual stress. Conversely, the diameter and spacing of the joints are positively proportional to the highest value. When the diameter of the solder joint is increased from 0.55 mm to 0.75 mm, the maximum residual stress in the BGA solder joint increases from 37.243 MPa to 36.835 MPa. Conversely, increasing the height of the solder joint from 0.36 mm to 0.44 mm reduces the stress from 39.776 MPa to 36.835 MPa.

Abstract Objective To assess the potential of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in monitoring renal changes in a diabetic nephropathy (DN) rat model with acute kidney injury (CI-AKI) induced by iso-osmotic contrast media (IOCM) and low-osmotic contrast media (LOCM). Methods A diabetic nephropathy rat model was established, and the animals were randomly split into the LOCM group and IOCM group (n = 13 per group), with iopamidol and iodixanol injection, respectively (4 g iodine/kg). MRI including IVIM and DKI was performed 24 h before contrast medium injections (baseline) and 1, 24, 48, and 72 h after injections. Changes in pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusion (MD), mean kurtosis (MK), serum creatinine (SCr) and urea nitrogen (BUN), histopathology alterations, and α-smooth muscle actin (α-SMA) expression were assessed. Inter-observer agreement was evaluated using the intraclass correlation coefficient (ICC). Results Compared against baseline levels, significant decreases in D, D*, and f were observed in all anatomical kidney compartments after contrast injection (p

Abstract Long non-coding RNA (lncRNA) was reported to be a critical regulator of cellular homeostasis, but poorly understood in idiopathic pulmonary fibrosis (IPF). Here, we systematically identified a crucial lncRNA, p53-induced long non-coding RNA TP53 target 1 (TP53TG1), which was the dysregulated hub gene in IPF regulatory network and one of the top degree genes and down-regulated in IPF-drived fibroblasts. Functional experiments revealed that overexpression of TP53TG1 attenuated the increased expression of fibronectin 1 (Fn1), Collagen 1α1, Collagen 3α1, ACTA2 mRNA, Fn1, and Collagen I protein level, excessive fibroblasts proliferation, migration and differentiation induced by TGF-β1 in MRC-5 as well as PMLFs. In vivo assays identified that forced expression of TP53TG1 by adeno-associated virus 5 (AAV5) not only prevented BLM-induced experimental fibrosis but also reversed established lung fibrosis in the murine model. Mechanistically, TP53TG1 was found to bind to amount of tight junction proteins. Importantly, we found that TP53TG1 binds to the Myosin Heavy Chain 9 (MYH9) to inhibit its protein expression and thus the MYH9-mediated activation of fibroblasts. Collectively, we identified the TP53TG1 as a master suppressor of fibroblast activation and IPF, which could be a potential hub for targeting treatment of the disease.

Abstract Mucin 3A (MUC3A) is overexpressed in colorectal cancer (CRC) and associated with poor prognosis, but the related mechanism remains unclear. Our study found that MUC3A promotes the progression of CRC by activating the PI3K/Akt/mTOR signaling pathway. Knockout of MUC3A significantly inhibited the proliferation of CRC cells and induced G1 phase arrest by upregulating p21 protein, an important cell cycle regulator. Moreover, knockout of MUC3A significantly inhibited invasion ability and enhanced the sensitivity to the chemotherapeutic agent 5-FU. Furthermore, we found that knockout of MUC3A repressed the PI3K/Akt/mTOR pathway through RNA-seq. Treatment with the PI3K/Akt/mTOR pathway inhibitor rapamycin successfully eliminated the difference in proliferation, invasion and chemoresistance between MUC3A knockout cells and control cells. Our study suggests that MUC3A is a potential oncogene that promotes the proliferation, invasion, and chemotherapy resistance of CRC. Moreover, CRC patients with high expression of MUC3A may benefit from rapamycin treatment.

Abstract Background Esophageal Squamous Cell Carcinoma (ESCC) was characterized as a regional-prevalent and aggressive tumor with high morbidity and mortality. NIMA-related kinase 2 (NEK2) is an interesting oncogene, the alteration of which leads to patients-beneficial outcomes. We aimed to explore the role of NEK2 in ESCC and excavate its mechanism. Methods RNA-seq data were downloaded from TCGA and GEO and analyzed by R software. The protein levels were detected by immunohistochemistry (IHC) or western blot (WB), and mRNA expression was detected by qRT-PCR. The in vitro role of proliferation and migration was detected by Transwell migration assay and by colony formation assay, respectively. The in vivo roles were explored using a subcutaneous xenograft tumor model, where immunofluorescence (IF) and IHC were employed to investigate expression and localization. The interaction between proteins was detected by immunoprecipitation. The stability of proteins was measured by WB in the presence of cycloheximide. Results A higher level of NEK2 was found in ESCC than normal esophageal epithelia in GEO, TCGA, and tissue microarray, which was associated with worse prognoses. The NEK2 knockdown impaired the proliferation and migration of ESCC, which also downregulated YAP1 and EMT markers like N-cadherin and Vimentin in vitro. On the contrary, NEK2 overexpression enhanced the migration of ESCC and elevated the levels of YAP1, N-cadherin, and Vimentin. Additionally, the overexpression of YAP1 in NEK2 knocked down ESCCs partly rescued the corresponding decrease in migration. The knockdown of NEK2 played an anti-tumor role in vivo and was accompanied by a lower level and nucleus shuffling of YAP1. In mechanism, NEK2 interacted with YAP1 and increased the stability of both endogenous and exogenous YAP1 by preventing ubiquitination. Moreover, the computer-predicted phosphorylation site of YAP1, Thr-143, reduced the ubiquitination of HA-YAP1, strengthened its stability, and thus influenced the migration in vitro. Conclusions NEK2 is a prognostic oncogene highly expressed in ESCC and promotes the progression of ESCC in vitro and in vivo. Mechanistically, NEK2-mediated phosphorylation of YAP1 at Thr-143 protects it from proteasome degradation and might serve as a promising therapeutic target in ESCC. Video Abstract

Measurement(s) aboveground biomass Technology Type(s) data assimilation

Abstract Background Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase ( 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT. Methods This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People’s Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety. Discussion This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT. Trial registration Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .

Measurement(s) human footprint Technology Type(s) remote sensing Factor Type(s) Built Environment • Population Density • Nighttime lights • Croplands • Pastures • Roads • Railways • Navigable waterways

Abstract Background The prevalence of anxiety and depression symptoms among caretakers of children with atopic dermatitis (AD) and associated factors is unclear. The study was designed to explore anxiety and depression symptoms among caretakers of AD, and screen factors associated with anxiety and depression symptoms. Methods A total of 901 children with AD and their caretakers were continuously enrolled and interviewed at dermatology department of Capital Institute of Pediatrics, Beijing, China. Children’s medication was administered by their caretakers. Caretakers’ anxiety and depression symptoms were evaluated by Hamilton Depression Rating Scale-17 and Hamilton Depression Rating Scale, while medication compliance was evaluated and divided into poor ( 7 points) by Morisky Medication Adherence Scale. Multilevel ordered logistic regression was used to screen factors associated with caretakers’ anxiety and depression. Results Among caretakers, 41.5% had anxiety symptoms, 39.6% had depression symptoms, 51.4% have any of the two and 29.7% had both of the two. Factors associated with caretakers’ anxiety symptoms included longer duration of the illness (OR, 0.99, 95% CI 0.98–0.99) and taking care of children with severe AD (OR, 2.55, 95% CI 1.43–4.55). Factors associated with caretakers’ depression symptoms included higher educational level (OR, 0.56, 95% CI 0.39–0.80), taking care of children with moderate (OR, 2.01, 95% CI 1.15–3.50) and severe AD (OR, 3.99, 95% CI 2.10–7.59) and poor medication compliance (OR, 3.45, 95% CI 1.13–10.56). Conclusions Prevalence of anxiety and depression symptoms among caretakers of AD were high. Attention should be paid to caretakers of AD at higher risk for those psychological problems.

Zao Chili (ZC) is a traditional fermented pepper, which plays an important role in Chinese cooking. The aim of this study was to elucidate the effect of Lactipllantbacillus plantarum 5-1 on the physicochemical properties, metabolite and microbiota profiling of ZC. The physicochemical factors changed regularly with the fermentation time. In the microbial communities, Lactobacillus, Weissella, Enterobacter, Gibberella, Fusarium, Zygosaccharomyces and Pichia were the dominant genera. 7 kinds of organic acids were detected in the whole fermentation process of ZC, but only 5 kinds changed significantly. Based on the OPLS-DA model with VIP > 1 and ANOVA with P

The Chishui River basin is the main production area of the sauce-flavor Baijiu. Due to the particularity of sauce-flavor Baijiu technology, a large site of workshops needs to be built for brewing and storage. Therefore, used the natural karst caves of Guizhou province to manufacture the sauce-flavor Baijiu, which has enriched the connotation of sauce-flavor Baijiu and saved valuable land resources. In this study, the fermentation grains in the seven stages during the Xiasha round of the cave-brewed sauce-flavor Baijiu (CBSB) were detected using a combination of physicochemical analysis, Headspace solid-phase microextraction gas chromatography-mass detection, and Illumina HiSeq sequencing methods. The results showed Unspecified_Leuconostocaceae, Weissella, Unspecified_Bacillaceae, Saccharomycopsis, Thermomyces, and Unspecified_Phaffomycetaceae were the main bacterial and fungal genera in the stacking fermentation (SF). In the cellar fermentation (CF), the Lactobacillus, Unspecified_Lactobacillaceae, Thermoactinomyces, Saccharomycopsis, Unspecified_Phaffomycetaceae, and Wickerhamomyces were the main bacterial and fungal genera. A total of 72 volatiles were detected in the fermented grains. Linear discriminant analysis Effect Size (LEfSe) identified 23 significantly different volatile metabolites in the fermentation process, including 7 esters, 6 alcohols, 4 acids, 3 phenols, 1 hydrocarbon, and 2 other compounds. Redundancy analysis was used to explore the correlation between dominant microbial genera and physicochemical properties. Starch was the main physicochemical property affecting microbial succession in the SF. Acidity, moisture, and reducing sugar were the main driving factors of microbial succession in the CF. The Pearson correlation coefficient revealed the correlation between dominant microbial genera and significantly different volatile flavor substances. A total of 18 dominant microbial genera were associated with significantly different volatile metabolites, Lactobacillus, Weissella, Wickerhamomyces, and Aspergillus were shown to play crucial roles in metabolite synthesis. On this basis, a metabolic map of the dominant microbial genera was established. This study provides a theoretical basis for the production and quality control of sauce-flavor Baijiu brewed in natural karst caves and lays a foundation for studying the link between flavor formation and microorganisms.

Northeast China is one of the most major grain banks in China and has an overwhelming influence on food security. To mitigate the challenges caused by increasing food demands and soil protection, crop rotation and fallowing policies have been introduced in Northeast China. These soil protection policies change annual crop planting area and crop distribution. To monitor crop type and its changes on a regional scale in time series, we explore the automatic sampling approach by hexagon strategy and tile-based classification by random forest (RF) algorithm using time-series Landsat-8 Operational Land Imager (OLI) images during 2013–2021. The crop maps have high credibility with the overall accuracies (OA) wall-to-wall ranging from 0.89 to 0.97, and also have close agreement with statistical data city by city. This study provides a highly reliable long-term crop maps dataset, which can be helpful for food security and regional agricultural production management.

Regulated cell death (RCD) contributes to reshaping the tumor immune microenvironment and participating in the progression of non-small cell lung cancer (NSCLC); however, related mechanisms have not been fully disclosed. Here, we identified 5 subclusters of NSCLC based on consensus clustering of 3429 RCD-associated genes in the TCGA database and depicted the genomic features and immune landscape of these clusters. Importantly, the clusters provided insights into recognizing tumor microenvironment (TME) and tumor responses to immunotherapy and chemotherapy. Further, we established and validated an RCD-Risk model based on RCD-associated genes, which strongly predicted the prognosis, TME, and immunotherapy outcomes in NSCLC patients. Notably, tissue microarray staining confirmed that the expression of LDLRAD3, a core gene in RCD-Risk model, correlated with poor survival. In conclusion, we developed a novel RCD classification system and RCD-Risk model of NSCLC, serving as a robust and promising predictor for prognosis and immunotherapy benefit of individual NSCLC patients.

Hydrocolloids have been widely used to adjust properties of natural starches, but related research on kudzu starch is still rare. In this study, we investigated the effects of gum arabic (AG), sodium alginate (SA), locust bean gum (LG), and guar gum (GG) on kudzu starch from the perspective of its particle size, pasting, texture, rheology, dehydration rate, thermal properties, microstructure, and sensitivity to amyloglucosidase. Results showed that GG significantly increased the particle size of starch. Addition of AG led to lower peak-, final- and holding-viscosity. SA increased the retention viscosity of kudzu starch, while LG and GG increased its peak viscosity. Addition of hydrocolloids increased the hardness, chewiness, and cohesiveness of starch-hydrocolloid complexes, and reduced the dehydration rate of complex gels. Dynamic rheological data showed that the energy storage modulus (G′) was significantly higher than the loss modulus (G″). The magnitude of modulus increased with frequency, and elastic properties were better than viscous properties. Thermal analysis showed that hydrocolloids increased the starting temperature (To), and the final temperature (Tc). With addition of each of these four hydrocolloids, a more regular and porous thick-wall dense structure was formed, which effectively lowered kudzu starch's sensitivity to amyloglucosidase. It indicated that the binding of hydrocolloid to starch may slow down glucose release into blood during digestion. These results will help understand effects of natural hydrocolloid on kudzu starch, as well as expanding its application in food industry.

IntroductionMechanical circulatory support (MCS) can help to maintain hemodynamic stability, improve cardiac function, reduce cardiac load, and is an important method for the treatment of advanced heart failure. However, traditional MCS systems [IABP, Impella, TandemHerat, veno-arterial extracorporeal membrane oxygenation (VA-ECMO)] are associated with limitations including trauma, a high rate of complications (hemolysis, bleeding) and require complex care from nurses.Case summaryWe report a case of left heart failure resulting from dilated cardiomyopathy in a 24 years-old man. A catheter was placed through the right jugular vein and a drainage tube was positioned under ultrasound guidance through the superior vena cava, right atrium, atrial septum, to the left atrium, and returned to the axillary artery using an extracorporeal magnetic levitation ventricular assist device (VAD). The patient was successfully supported for 10 days and bridged to heart transplant.DiscussionTo the best of our knowledge, this is the first report of the use of an extracorporeal magnetic levitation VAD for MCS via a percutaneous approach. Our findings support the wider use of this strategy for patients awaiting myocardial recovery or who require heart bridging or transplantation.

Abstract Background The hyperdense middle cerebral artery sign (HMCAS) is an early radiological marker to provide an early diagnosis and to identify ischemia. As reported, HMCAS is associated with heavy clot burden. Moreover, a heavy clot burden may cause obstruction of the orifices of arteries for leptomeningeal collateral flows and can lead to severe clinical conditions. However, the direct relationship between HMCAS and collateral flows remains unclear. Therefore, we explored the association between HMCAS and leptomeningeal collaterals in patients with acute ischemic stroke. Methods Consecutive ischemic stroke patients were enrolled from January 2015 to April 2021. HMCAS appearance and collateral status were detected by multimodal computed tomography at admission. Logistic regression analyses helped to identify the association between HMCAS, collateral flows and stroke severity. Results In 494 included patients, 180 (36.4%) presented with HMCAS. Ipsilateral collaterals were not seen or less prominent in patients with HMCAS (P

Ion binding proteins (IBPs) can selectively and non-covalently interact with ions. IBPs in phages also play an important role in biological processes. Therefore, accurate identification of IBPs is necessary for understanding their biological functions and molecular mechanisms that involve binding to ions. Since molecular biology experimental methods are still labor-intensive and cost-ineffective in identifying IBPs, it is helpful to develop computational methods to identify IBPs quickly and efficiently. In this work, a random forest (RF)-based model was constructed to quickly identify IBPs. Based on the protein sequence information and residues’ physicochemical properties, the dipeptide composition combined with the physicochemical correlation between two residues were proposed for the extraction of features. A feature selection technique called analysis of variance (ANOVA) was used to exclude redundant information. By comparing with other classified methods, we demonstrated that our method could identify IBPs accurately. Based on the model, a Python package named IBPred was built with the source code which can be accessed at https://github.com/ShishiYuan/IBPred.

Evapotranspiration (ET) is an important component of terrestrial ecosystems and is sensitive to climate and land-use change due to its obvious link to ecohydrological processes. Therefore, understanding the spatiotemporal variability of evapotranspiration and its drivers under different land cover types plays an important role in estimating the impact of environmental change on the regional water cycle. In this study, we first estimated the spatiotemporal variations of ET for different land cover types in the Yunnan Province from 2001 to 2020 using the MODIS-Terra ET product (MOD16A2.06) and meteorological datasets, and quantified the contribution of six factors: namely, temperature (TEMP), precipitation (PRCP), relative humidity (RH), wind speed (WDSP), soil moisture (SLME), NDVI, elevation, and slope, to the ET under different land cover types by using a ridge regression model. We then discussed the main reasons for the differences in ET in the Yunnan Province under different land cover types. The conclusions are as follows: during the study period, the annual mean ET ranged from 27 to 1183 mm, and there was a large spatial heterogeneity in its spatial distribution, with the smallest increasing trend of 2.1 mm/year in agricultural land and the largest increasing trend of 4.7 mm/year in grassland. Except for cropland, the sum of the relative contributions of the three influence factors, precipitation (PRCP), NDVI, and elevation, to all land cover types exceeded 40%, making them the most dominant factors influencing ET changes in the Yunnan Province. This study provides a comprehensive assessment of the impacts of climate, vegetation, topography, and soils on ET, and contributes to the development of appropriate water resource management policies for different subsurface types in the context of climate warming and revegetation programs.

The optimization of micropropagation for blueberries is crucial due to the growing blueberry industry and demand for plantlets. This study focused on four stages: explant sterilization, in vitro establishment, in vitro proliferation, and ex vitro rooting, aiming to establish an efficient in vitro propagation system for southern highbush blueberry cultivar ‘ZY09’. The most effective explant sterilization method was a 60 s treatment with 75% ethanol and a 5 min treatment with 4% NaClO. During the establishment of the in vitro culture, the modified woody plant medium was found to be suitable. The replacement of NH4NO3 in woody plant medium with (NH4)2SO4 facilitated the proliferation of blueberry microshoots. The optimal combination of plant growth regulators for the in vitro proliferation of blueberry microshoots was indole-3-butyric acid (0.1 mg·L−1), thidiazuron (0.0005 mg·L−1), and zeatin (1 mg·L−1). Perlite was the most suitable substrate for ex vitro rooting. The best ex vitro rooting performance was observed without immersion in growth regulators. Indole-3-butyric acid enhances root formation and suppresses root elongation in blueberries. The findings of this study can be applied to large-scale in vitro propagation of southern highbush blueberry and provide a reference for the genetic transformation of blueberries.

Flowering Chinese cabbage (Brassica campestris L. ssp. Chinensis var. utilis Tsen et Lee) is a widely consumed vegetable in southern China with significant economic value. Developing product organs in the flowering Chinese cabbage involves two key processes: bolting and flowering. Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor known for its crucial role in various plant developmental processes. However, there is limited information available on the involvement of this gene family during flowering during Chinese cabbage development. In this study, 49 BcNF-Y genes were identified and characterized along with their physicochemical properties, gene structure, chromosomal location, collinearity, and expression patterns. We also conducted subcellular localization, yeast two-hybrid, and transcriptional activity assays on selected BcNF-Y genes. The findings of this study revealed enhanced expression levels of specific BcNF-Y genes during the stalk development and flowering stages in flowering Chinese cabbage. Notably, BcNF-YA8, BcNF-YB14, BcNF-YB20, and BcNF-YC5 interacted with BcRGA1, a negative regulator of GA signaling, indicating their potential involvement in GA-mediated stalk development. This study provides valuable insights into the role of BcNF-Y genes in flowering Chinese cabbage development and suggests that they are potential candidates for further investigating the key regulators of cabbage bolting and flowering.

Injectable hydrogels possess tremendous merits for use in muscle regeneration; however, they still lack intrinsic biological cues (such as the proliferation and differentiation of myogenic cells), thus considerably restricting their potential for therapeutic use. Herein, we developed a double cross-linked injectable hydrogel composed of methacrylamidated oxidized hyaluronic acid (MOHA) and muscular decellularized matrix (MDM). The chemical composition of the hydrogel was confirmed using 1H NMR and Fourier transform infrared spectroscopy. To achieve cross-linking, the aldehyde groups in MOHA were initially reacted with the amino groups in MDM through a Schiff-based reaction. This relatively weak cross-linking provided the MOHA/MDM hydrogel with satisfactory injectability. Furthermore, the methacrylation of MOHA facilitated a second cross-linking mechanism via UV irradiation, resulting in improved gelation ability, biomechanical properties, and swelling performance. When C2C12 myogenic cells were loaded into the hydrogel, our results showed that the addition of MDM significantly enhanced myoblast proliferation compared to the MOHA hydrogel, as demonstrated by live/dead staining and Cell Counting Kit-8 assay after seven days of in vitro cultivation. In addition, gene expression analysis using quantitative polymerase chain reaction indicated that the MOHA/MDM hydrogel promoted myogenic differentiation of C2C12 cells more effectively than the MOHA hydrogel, as evidenced by elevated expression levels of myogenin, troponin T, and MHC in the MOHA/MDM hydrogel group. Moreover, after four to eight weeks of implantation in a full-thickness abdominal wall-defect model, the MOHA/MDM hydrogel could promote the reconstruction and repair of functional skeletal muscle tissue with enhanced tetanic force and tensile strength. This study provides a new double cross-linked injectable hydrogel for use in muscular tissue engineering.

Marine flow-passing components are susceptible to cavitation erosion (CE), and researchers have worked to find ways to reduce its effects. Laser Shock Peening (LSP), a material strengthening method, has been widely used in aerospace and other cutting-edge fields. In recent years, LSP has been used in cavitation resistance research. However, the current LSP research does not realize a comprehensive predictive assessment of the material’s CE resistance. This paper uses m stresses to develop a comprehensive set of strengthening effect prediction models from LSP to CE using finite element analysis (FEA). Results show that the LSP-1 sample (4 mm spot, 10 J energy) introduced a compressive residual stress value of 37.4 MPa, better than that of 16.6 MPa with the LSP-2 sample (6 mm spot, 10 J energy), which is generally consistent with the experimental findings; the model predicts a 16.35% improvement in the resistance of LSP-1 sample to water jet damage, which is comparable to the experimental result of 14.02%; additionally, interactions between micro-jets do not predominate the cavitation erosion process and the final CE effect of the material is mainly due to the accumulation of jet-material interaction.

Abstract Background Ultrasound examination can be applied to the diagnosis of pediatric elbow fracture. This study aims to analyze the application value of ultrasound in the surgical treatment of supracondylar humeral fractures. Methods 64 children with supracondylar humeral fractures were treated with ultrasound-guided closed reduction and percutaneous pinning (CRPP), 31 patients were treated with CRPP under radiography guidence. The reduction effect of supracondylar humeral fractures was determined through the perioperative ultrasound images of the lateral, medial and posterior aspects of the elbow. Percutaneous pinning was performed after supracondylar humeral fractures were well reduced. A follow-up examination was performed and all the patients were evaluated according to Flynn’s criteria. Results The mean duration of surgery was 58.3 min (42–108 min) in the ultrasound group and 41.5 min (24-63 min) in the radiography group (P 0.05). After surgery, three patients had pin tract infection. One patient had ulnar nerve neurapraxia in the radiography group. No cases with Volkmann’s contracture were reported. Conclusion Ultrasound-guided CRPP is a safe and reliable surgical treatment of pediatric supracondylar humeral fractures. Trial registration Retrospectively registered.

Summary: Background: More effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines. Methods: This randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 μg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 μg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 μg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758. Findings: Between January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines. Interpretation: Although all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant. Funding: Yunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Double First-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

BackgroundAs an emerging technology, virtual reality (VR) has been broadly applied in the medical field, especially in neurorehabilitation. The growing application of VR therapy promotes an increasing amount of clinical studies. In this paper, we present a bibliometric analysis of the existing studies to reveal the current research hotspots and guide future research directions.MethodsArticles and reviews on the related topic were retrieved from the Science Citation Index Expanded of Web of Science Core Collection database. VOSviewer and Citespace software were applied to systematically analyze information about publications, countries, institutions, authors, journals, citations, and keywords from the included studies.ResultsA total of 1,556 papers published between 1995 and 2021 were identified. The annual number of papers increased gradually over the past three decades, with a peak publication year in 2021 (n = 276). Countries and institutions from North America and Western European were playing leading roles in publications and total citations. Current hotspots were focused on the effectiveness of VR therapy in cognitive and upper limb motor rehabilitation. The clusters of keywords contained the four targeted neurological diseases of VR, while the burst keywords represented that the latest studies were directed toward more defined types of VR therapy and greater study design.ConclusionsOur study offers information regarding to the current hotspots and emerging trends in the VR for rehabilitation field. It could guide future research and application of VR therapy in neurorehabilitation.

Gibberellin and cytokinin synergistically regulate the stalk development in flowering Chinese cabbage. KNOX proteins were reported to function as important regulators of the shoot apex to promote meristem activity by synchronously inducing CTK and suppressing GA biosynthesis, while their regulatory mechanism in the bolting and flowering is unknown. In this study, 9 BcKNOX genes were identified and mapped unevenly on 6 out of 10 flowering Chinese cabbage chromosomes. The BcKNOXs were divided into three subfamilies on the basis of sequences and gene structure. The proteins contain four conserved domains except for BcKNATM. Three BcKNOX TFs (BcKNOX1, BcKNOX3, and BcKNOX5) displayed high transcription levels on tested tissues at various stages. The major part of BcKNOX genes showed preferential expression patterns in response to low-temperature, zeatin (ZT), and GA3 treatment, indicating that they were involved in bud differentiation and bolting. BcKNOX1 and BcKNOX5 showed high correlation level with gibberellins synthetase, and CTK metabolic genes. BcKONX1 also showed high correlation coefficients within BcRGA1 and BcRGL1 which are negative regulators of GA signaling. In addition, BcKNOX1 interacted with BcRGA1 and BcRGL1, as confirmed by yeast two-hybrid (Y2H) and biomolecular fluorescence complementation assay (BiFC). This analysis has provided useful foundation for the future functional roles’ analysis of flowering Chinese cabbage KNOX genes

Millennial employees are increasingly paying more attention to well-being in the workplace and it has become an important issue for managers. Given that millennial employees are more sensitive to ethical issues, this study began by analyzing an ethical element in the organization—the ethical climate—and explored whether millennial employees have higher affective well-being in organizations with a good ethical climate. We verified our hypotheses based on 288 valid questionnaires collected from 40 teams. The results showed that: (1) ethical climate was a positive predictor of millennial employees’ organizational citizenship behavior (OCB) and affective well-being, (2) employees’ OCB partially mediated the relationship between ethical climate and affective well-being, and (3) an employee’s moral identity effectively moderated the relationship between ethical climate and affective well-being, although it did not play a significant moderating role between ethical climate and OCB. These findings provide empirical support for applying situational strength and social information processing theories and emphasize the importance of cultivating an ethical climate in organizations.

Adeno-associated virus (AAV)-mediated gene transfer is an efficient method of gene over-expression in the vestibular end organs. However, AAV has limited usefulness for delivering a large gene, or multiple genes, due to its small packaging capacity (< 5 kb). Co-transduction of dual-AAV vectors can be used to increase the packaging capacity for gene delivery to various organs and tissues. However, its usefulness has not been well validated in the vestibular sensory epithelium. In the present study, we characterized the co-transduction of dual-AAV vectors in mouse utricles following inoculation of two AAV-serotype inner ear (AAV-ie) vectors via canalostomy. Firstly, co-transduction efficiencies were compared between dual-AAV-ie vectors using two different promoters: cytomegalovirus (CMV) and CMV early enhancer/chicken β-actin (CAG). In the group of dual AAV-ie-CAG vectors, the co-transduction rates for striolar hair cells (HCs), extrastriolar HCs, striolar supporting cells (SCs), and extrastriolar SCs were 23.14 ± 2.25%, 27.05 ± 2.10%, 57.65 ± 7.21%, and 60.33 ± 5.69%, respectively. The co-transduction rates in the group of dual AAV-ie-CMV vectors were comparable to those in the dual AAV-ie-CAG group. Next, we examined the co-transduction of dual-AAV-ie-CAG vectors in the utricles of neonatal mice and damaged adult mice. In the neonatal mice, co-transduction rates were 52.88 ± 3.11% and 44.93 ± 2.06% in the striolar and extrastriolar HCs, respectively, which were significantly higher than those in adult mice. In the Pou4f3+/DTR mice, following diphtheria toxin administration, which eliminated most HCs and spared the SCs, the co-transduction rate of SCs was not significantly different to that of normal utricles. Transgene expression persisted for up to 3 months in the adult mice. Furthermore, sequential administration of two AAV-ie-CAG vectors at an interval of 1 week resulted in a higher co-transduction rate in HCs than concurrent delivery. The auditory brainstem responses and swim tests did not reveal any disruption of auditory or vestibular function after co-transduction with dual-AAV-ie vectors. In conclusion, dual-AAV-ie vectors allow efficient co-transduction in the vestibular sensory epithelium and facilitate the delivery of large or multiple genes for vestibular gene therapy.

Glycine-rich proteins (GRPs) are a large family of proteins that play vital roles in cell wall remodeling, metabolism and development, and abiotic stress response. Although the functions of GRPs in cell wall remodeling have been extensively characterized, only a few studies have explored their effects on chlorophyll metabolism and hormone response. Accordingly, we aimed to determine the molecular mechanism of BcGRP23 and its role in chlorophyll metabolism and the BRI1-EMS-SUPPRESSOR 1 (BES1) signaling pathway in flowering Chinese cabbage. The expression levels of BcGRP23 in the leaves and stems gradually decreased with increasing growth and development of flowering Chinese cabbage, while BcGRP23 was barely expressed after flowering. As plant growth continued, the GUS (β-glucuronidase) stain gradually became lighter in hypocotyls and was largely free of growth points. The petioles and stems of BcGRP23-silenced plants lost their green color, and the contents of chlorophyll a (Chl a) and Chl b were significantly reduced. Further research revealed that the expression levels of chlorophyll degradation-related genes were significantly increased in silenced plants compared with the control; however, the opposite was noted for the BcGRP23-overexpressing lines. The BcGRP23 promoter sequence contains numerous hormone-responsive elements. In fact, the expression of BcGRP23 was upregulated in flowering Chinese cabbage following treatment with the hormones indole-3-acetic acid (IAA), gibberellin (GA), 6-benzylaminopurine (6-BA), methyl jasmonate (MeJA), and brassinosteroid (BR). Treatment with BR led to the most significant upregulation. BES1, in response to BRs, directly activated the BcGRP23 promoter. Overall, BcGRP23 regulated the expression of chlorophyll degradation-related genes, thereby affecting the chlorophyll content. Furthermore, the expression of BcGRP23 was significantly regulated by exogenous BR application and was directly activated by BES1. These findings preliminarily suggest the molecular mechanism and regulatory pathway of BcGRP23 in the growth and development of flowering Chinese cabbage plants and their response to environmental stress.

Abstract Current interpretations of the LHC results on two Higgs doublet models (2HDM) underestimate the sensitivity due to neglecting higher order effects. In this work, we revisit the impact of these effects using the current cross-section times branching ratio limits of the $$A\rightarrow hZ, H \rightarrow VV$$ A → h Z , H → V V and $$H\rightarrow hh$$ H → h h channels. With a degenerate heavy Higgs mass $$m_\varPhi $$ m Φ , we find that the LHC searches gain sensitivity to the small $$\tan \beta $$ tan β region after including loop corrections, even close to $$\cos (\beta -\alpha )=0$$ cos ( β - α ) = 0 which is not reachable at tree level for all types of 2HDM. For a benchmark point with $$m_\varPhi =300$$ m Φ = 300 GeV, $$\tan \beta

Cellular automata (CA)-based models have been extensively used in urban expansion modeling because of their simplicity, flexibility and intuitiveness. Previous studies on CA-based urban growth modeling have mainly focused on the process of spatial allocation of increased urban lands; however, the temporal contexts during the simulation have not been properly explored. In this study, we examined the influence of temporal contexts of initial seeds (i.e. urban extent maps), transition rules, and urban demands (i.e. urban areas) on the CA-based urban growth modeling in Beijing, China, over a long period of 1984–2013. Comparison of the annual model outputs with the time series data of annual urban extent maps from satellite observations revealed that the overall accuracy of urban growth modeling decreased by approximately 12%, with an increase in iterations from 1984–2013. By contrast, the value of the figure of merit (FoM) increased to 26.57%. The continuous change of FoM during the modeling suggests a “spin-up” effect, a rapid increase in FoM at the beginning of modeling, of CA-based urban growth models, and this effect is primarily attributed to the neighborhood component in CA. The effect of temporal contexts reflected by components of initial seeds and urban demands in CA-based urban growth models have considerable impacts on the model performance, i.e. the FoM increased by 7% when using actual urban demands during each iteration instead of the commonly used linear growth during the modeling period. Hence, we suggest that more efforts regarding the temporal contexts in CA-based modeling are required, to better understand error propagation and uncertainty assessment.

Compacted bentonite/sand mixture have been considered as possible sealing/backfilling material in the deep geological disposal of high-level radioactive nuclear waste. The swelling pressure of the compacted bentonite/sand mixture is of significance in the design of the geological repository, which requires good consistency between data obtained by laboratory and field measurement. In this work, a series of swelling pressure tests were performed on compacted MX80 bentonite/sand specimens prepared by methods commonly adopted in laboratory (As-compacted, Transferred) and those mimicking the real block manufacturing process (Trimmed, Inserted). Results shown that with identical dry density (especially when the dry density was larger than 1.70 Mg/m3), largest swelling pressure was obtained in specimens prepared by method Inserted, followed by method As-compacted, Transferred and Trimmed. The distinct difference between the swelling pressure could be largely attributed to the effects of residual post-compaction lateral stress. More interestingly, specimens prepared by methods Trimmed and Transferred followed a similar swelling pressure-dry density relationship. From this point of view, method Transferred without causing mass loss, change of bentonite content and possible technological voids effect was recommended in lieu of method Trimmed for specimen preparation in laboratory.

Abstract Background Lipid phosphate phosphatases (LPP) are critical for regulating the production and degradation of phosphatidic acid (PA), an essential signaling molecule under stress conditions. Thus far, the LPP family genes have not been reported in rapeseed (Brassica napus L.). Results In this study, a genome-wide analysis was carried out to identify LPP family genes in rapeseed that respond to different stress conditions. Eleven BnLPPs genes were identified in the rapeseed genome. Based on phylogenetic and synteny analysis, BnLPPs were classified into four groups (Group I-Group IV). Gene structure and conserved motif analysis showed that similar intron/exon and motifs patterns occur in the same group. By evaluating cis-elements in the promoters, we recognized six hormone- and seven stress-responsive elements. Further, six putative miRNAs were identified targeting three BnLPP genes. Gene ontology analysis disclosed that BnLPP genes were closely associated with phosphatase/hydrolase activity, membrane parts, phosphorus metabolic process, and dephosphorylation. The qRT-PCR based expression profiles of BnLPP genes varied in different tissues/organs. Likewise, several gene expression were significantly up-regulated under NaCl, PEG, cold, ABA, GA, IAA, and KT treatments. Conclusions This is the first report to describe the comprehensive genome-wide analysis of the rapeseed LPP gene family. We identified different phytohormones and abiotic stress-associated genes that could help in enlightening the plant tolerance against phytohormones and abiotic stresses. The findings unlocked new gaps for the functional verification of the BnLPP gene family during stresses, leading to rapeseed improvement.

Abstract Background The very high burden of rifampicin resistance tuberculosis (RR-TB) and the very low detection of RR-TB cases are a major challenge that China has been facing. This study analyzed the characteristics of RR-TB detection in China after the change of RR-TB detection strategy since 2015, aiming to provide reference and evidence for the development of more precise national drug resistance tuberculosis prevention and control policy. Methods We extracted data related to rifampicin resistance screening from the national Tuberculosis Information Management System (TBIMS) from 2015 to 2019, and used descriptive research methods to analyze the screening rate of presumptive RR-TB, the number and duration of RR-TB patients detected and drug resistance testing methods in each year. Chi-square test was used to compare the differences in component ratio or rate between years, and Kruskal Wallis test was used to compare the differences in median days for detection of RR-TB patients in each year. Results A total of 68,200 RR-TB cases were detected during 2015–2019, of which 48.1% were new cases. The number and detection rate of RR-TB cases increased year by year, from 10 019 and 14.3% in 2015 to 18 623 and 28.7% in 2019, respectively. Of the bacteriologically confirmed TB cases, 81.9% were tested for RR in 2019, a considerable increase from 29.5% in 2015. In 2019, only 41.0% of RR-TB cases had fluoroquinolones (FQs) susceptibility testing performed, and this proportion has been declining year by year since 2016. The proportion of application of rapid molecular tools increased from 24.0% in 2015 to 67.1% in 2019, and the median days to obtain RR results was significantly shortened. In 2019, 76.0% of RR-TB cases were diagnosed as presumptive RR-TB in county-level hospitals. Conclusions After China modified the RR-TB detection strategy, the screening rate of RR and the number of RR-TB cases increased significantly. The RR testing methods now predominantly utilize rapid molecular tools. However, comprehensive measures should be implemented to close the gap in the detection of RR-TB cases. It is imperative to take FQs susceptibility testing seriously and effectively strengthen the laboratory capacity of county-level hospitals. Graphical Abstract

Abstract Background Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by inflammation of the synovial membrane. However, the etiology and underlying molecular events of RA are unclear. Here, we applied bioinformatics analysis to identify the key genes involved in RA. Methods GSE77298 was downloaded from the Gene Expression Omnibus (GEO) database. We used the R software screen the differentially expressed genes (DEGs). Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed by using the DAVID online tool. The STRING database was used to analyze the interaction of differentially encoded proteins. PPI interaction network was divided into subnetworks using MCODE algorithm and was analyzed using Cytoscape. Gene set enrichment analysis (GSEA) was performed to identify relevant biological functions. qRT-PCR analysis was also performed to verify the expression of identified hub DEGs. Results A total of 4062 differentially expressed genes were selected, including 1847 upregulated genes and 2215 downregulated genes. In the biological process, DEGs were mainly concentrated in the fields of muscle filament sliding, muscle contraction, intracellular signal transduction, cardiac muscle contraction, signal transduction, and skeletal muscle tissue development. In the cellular components, DEGs were mainly concentrated in the parts of cytosol, Z disk, membrane, extracellular exosome, mitochondrion, and M band. In molecular functions, DEGs were mainly concentrated in protein binding, structural constituent of muscle, actin binding, and actin filament binding. KEGG pathway analysis shows that DEGs mainly focuses on pathways about lysosome, Wnt/β-catenin signaling pathway, and NF-κB signaling pathway. CXCR3, GNB4, and CXCL16 were identified as the core genes that involved in the progression of RA. By qRT-PCR analysis, we found that CXCR3, GNB4, and CXCL16 were significantly upregulated in RA tissue as compared to healthy controls. Conclusion In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the progression of RA, and provide candidate targets for diagnosis and treatment of RA.

It is imperative to rapidly and precisely acquire crop lodging area and severity for disaster prevention and yield prediction. However, estimation of crop lodging area at a large scale remains challenging due to the relatively low sensitivity of remote sensing signal to the lodging variation, limited availability of remote sensing images, and lodging statistical data. This study proposes a new method for lodging area estimation based on the optimal grid cell of Sentinel-2 and crop lodging percentage, overcoming the limitation of traditional pixel-based mapping approaches that fail to obtain quantitative lodging information. Basing the spatial aggregation method, we analyzed the optimal grid size of Sentinel-2 data for lodging percentage estimation. Then we investigated the spectral response for different lodging percentage levels and analyzed the potential of lodging percentage estimation for Sentinel-2 metrics (including selected spectral bands and their derived vegetation indexes (VIs)). A quantitative model was established between the training set and the Sentinel-2 metrics using the random forest (RF) algorithm. Finally, around 1462.62 ha fields from six counties or districts in Heilongjiang province in China were estimated for lodging percentage. Results indicate that the proposed method can estimate the crop lodging percentage on the testing set with an R2 and RMSE of 0.64 and 25.24, respectively, which can explain around 95 % spatial variation of lodging crop. Moreover, the overall magnitude of reflectance increased with the increase in lodging percentage. Among all Sentinel-2 optimal metrics, the Green, SWIR1, and Red edge 1 bands are the most crucial indicators for lodging percentage estimation. Our results on lodging percentage estimation in the study area indicate that there is more lodging maize in the Meilisidawoerzu district than in other areas. Although typhoons passed over Fuyu and Lindian counties, the lodging percentage in these areas is relatively low. The lodging percentage map has great value in agriculture management and insurance claim.