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Hexavalent chromium [Cr(VI)]-contaminated soils have introduced a serious problem in China. Cr(VI) is hazardous to both the environment and public health and may degrade the engineering properties of soils. Accordingly, the effects of Cr(VI) on the physicochemical, mechanical, and microstructure properties of Chinese clay were investigated in this study. Results show that Cr(VI) had a considerable negative effect on the physicochemical, mechanical, and microstructure properties of soil. Specifically, Cr(VI) changed the physicochemical properties and degraded the mechanical properties of soil, led to the aggregation of soil particles, and created a large void space. Cr(VI) also changed the mineral composition of the soil and converted clay minerals into calcite. The changes in the microstructure and mineral composition of the soil were the primary reasons for the differences in the engineering properties of Cr(VI)-contaminated soil.

Calcium polysulfide (CaS5) is widely used in stabilizing Cr(VI)-contaminated soils. The stability properties of Cr(VI) and Cr are the most important indexes for evaluating the effectiveness of stabilized soil. This study investigated the effect of CaS5 dosage and curing age on the stability properties of Cr(VI) and Cr in contaminated soils and the relationship between leachability and Cr speciation. Results show that increasing the CaS5 dosage and curing age could improve the stability properties of Cr in stabilized soil. The leachability and Cr(VI) content in the stabilized soil significantly decreased along with increasing CaS5 dosage and curing age. The changes in the leachability of the soil were attributed to the changes in the Cr speciation distribution and microstructure of the stabilized soil. The exchangeable fraction was mainly converted into an oxidizable fraction, and a dense structure (ettringite and elemental sulphur) was formed along with increasing CaS5 dosage and curing age. The exchangeable and reducible fractions depended on Cr leachability, and the Cr in the synthetic precipitation leaching procedures predominantly resulted from the exchangeable and reducible fractions.

Background: As the most common types of pulmonary arterial hypertension (PAH) in childhood, the similarities and differences in clinical characteristics and prognosis between idiopathic PAH (IPAH) and PAH associated with congenital heart disease (PAH-CHD) are not well-known. This study describes and compares clinical features of pediatric IPAH and PAH-CHD in a single center of China during an 11-year period and explores the prognostic factors.Methods: Twenty-five children with IPAH and 60 children with PAH-CHD, diagnosed in West China Second Hospital of Sichuan University from January 2008 to December 2018, were chosen as study objects. The follow-up deadline was June 2019, and the end-point was all-cause death. The baseline data, results of auxiliary examinations, treatment strategies, and follow-up outcomes were recorded and compared between IPAH and PAH-CHD patients to explore the similarities, differences, and prognostic factors.Results: The median diagnostic age for PAH-CHD patients was 2.3 years, which was younger than IPAH patients (7.3 years; p = 0.009). Sixty-eight percent of the IPAH patients presented with exercise-induced symptoms at initial diagnosis, whereas 58.3% of the PAH-CHD patients were asymptomatic (p < 0.001). Sixty percent of the IPAH patients were in World Health Organization-functional class (WHO-FC) III or IV, which was significantly worse than those of the PAH-CHD patients (p = 0.002). The incidence of ST-segment and T-wave (ST-T) change in children with IPAH (76.0%) was significantly higher than that (28.3%) in children with PAH-CHD (p < 0.001). Mean corpuscular volume (MCV), mean platelet volume (MPV), and platelet distribution width were larger in IPAH patients than those in PAH-CHD patients (p < 0.01). The 1-, 3-, and 5-year survival rates of IPAH and PAH-CHD patients were 53.5, 46.5, and 31.2% and 96.5, 93.1, and 77.6%, respectively (p < 0.05). WHO-FC III-IV [relative risk (RR) = 2.750, p = 0.008] and higher MPV (RR = 1.657, p = 0.006) predicted poor prognosis for pediatric PAH.Conclusion: We showed that there are more differences than similarities between IPAH and PAH-CHD patients in clinical characteristics. PAH-CHD patients have a better prognosis than IPAH patients. WHO-FC III-IV and higher MPV at initial diagnosis are independent risk factors for poor prognosis.

Abstract Background Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p

Abstract Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

Abstract Background Cliffs are recognized as one of the most challenging environments for plants, characterized by harsh conditions such as drought, infertile soil, and steep terrain. However, they surprisingly host ancient and diverse plant communities and play a crucial role in protecting biodiversity. The Taihang Mountains, which act as a natural boundary in eastern China, support a rich variety of plant species, including many unique to cliff habitats. However, it is little known how cliff plants adapt to harsh habitats and the demographic history in this region. Results To better understand the demographic history and adaptation of cliff plants in this area, we analyzed the chromosome-level genome of a representative cliff plant, T. rupestris var. ciliata, which has a genome size of 769.5 Mb, with a scaffold N50 of 104.92 Mb. The rapid expansion of transposable elements may have contributed to the increasing genome and its ability to adapt to unique and challenging cliff habitats. Comparative analysis of the genome evolution between Taihangia and non-cliff plants in Rosaceae revealed a significant expansion of gene families associated with oxidative phosphorylation, which is likely a response to the abiotic stresses faced by cliff plants. This expansion may explain the long-term adaptation of Taihangia to harsh cliff environments. The effective population size of the two varieties has continuously decreased due to climatic fluctuations during the Quaternary period. Furthermore, significant differences in gene expression between the two varieties may explain the varied leaf phenotypes and adaptations to harsh conditions in different natural distributions. Conclusion Our study highlights the extraordinary adaptation of T. rupestris var. ciliata, shedding light on the evolution of cliff plants worldwide.

Summary: Background: SLC7A9 is responsible for the exchange of dibasic amino acids and cystine (influx) for neutral amino acids (efflux). Cystine/cysteine transport is related to ferroptosis. Methods: Sanger sequencing detected TP53 status of cancer cells. Transcriptomic sequencing and untargeted metabolome profiling were used to identify differentially expressed genes and metabolites, respectively, upon SLC7A9 overexpression. CCK8, cell clonality, and EdU assays were used to observe cell proliferation. Cystine probes, glutathione (GSH) probes, and lipid ROS probes were used to examine cystine, GSH, and lipid ROS levels. 13C metabolic flow assays were used to monitor cellular cystine and GSH metabolism. Patient-derived organoids (PDO), immunocompetent MFC mice allograft models and patient-derived xenograft (PDX) models were used to evaluate SLC7A9 impact on chemotherapeutic response and to observe therapeutic effect of SLC7A9 knockdown. Findings: Elevated SLC7A9 expression levels in gastric cancer cells were attributed to p53 loss. SLC7A9 knockdown suppressed the proliferation and increased the chemotherapy sensitivity of the cells. Chemotherapy was more effective in PDX and immunocompetent mice models upon SLC7A9 knockdown. Differentially expressed genes and metabolites between the SLC7A9 overexpression and control groups were associated with ferroptosis and GSH metabolism. SLC7A9 knockdown reduced cystine transport into cells, hampered intracellular cystine and GSH metabolic flow, decreased GSH synthesis, and increased lipid ROS levels in gastric cancer cells. Erastin was more effective at inducing ferroptosis in PDO and PDX models upon SLC7A9 knockdown. Interpretation: SLC7A9 promotes gastric cancer progression by acting as a suppressor of ferroptosis, independent of SLC7A11, which is negatively regulated by p53. Funding: This work was supported by National Natural Science Foundation of China, Innovation Promotion Program of NHC and Shanghai Key Labs SIBPT, and Shanghai Academy of Science & Technology.

Abstract Introduction The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. Methods This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. Results A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74–18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60–3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58–3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Conclusion Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Abstract Background The recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome. Methods Whole genome methylation sequencing of cfDNA was performed for 20 healthy individuals, 20 cases with non-hospitalized COVID-19 and 12 cases with severe COVID-19 admitted to intensive care unit (ICU). Differentially methylated regions (DMRs) and gene ontology pathway enrichment analyses were performed to explore the locus-specific methylation difference between cohorts. The proportion of cfDNA derived from lung and immune cells to a given sample (i.e. tissue fraction) at cell-type resolution was estimated using a novel algorithm, which reflects lung injuries and immune response in COVID-19 patients and was further used to evaluate clinical severity and patient outcome. Results COVID‑19 patients had globally reduced cfDNA methylation level compared with healthy controls. Compared with non-hospitalized COVID-19 patients, the cfDNA methylation pattern was significantly altered in severe patients with the identification of 11,156 DMRs, which were mainly enriched in pathways related to immune response. Markedly elevated levels of cfDNA derived from lung and more specifically alveolar epithelial cells, bronchial epithelial cells, and lung endothelial cells were observed in COVID-19 patients compared with healthy controls. Compared with non-hospitalized patients or healthy controls, severe COVID-19 had significantly higher cfDNA derived from B cells, T cells and granulocytes and lower cfDNA from natural killer cells. Moreover, cfDNA derived from alveolar epithelial cells had the optimal performance to differentiate COVID-19 with different severities, lung injury levels, SOFA scores and in-hospital deaths, with the area under the receiver operating characteristic curve of 0.958, 0.941, 0.919 and 0.955, respectively. Conclusion Severe COVID-19 has a distinct cfDNA methylation signature compared with non-hospitalized COVID-19 and healthy controls. Cell type-specific cfDNA methylation signature enables the tracing of COVID-19 related cell deaths in lung and immune cells at cell-type resolution, which is correlated with clinical severities and outcomes, and has extensive application prospects to evaluate tissue injuries in diseases with multi-organ dysfunction.

Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010–37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.

Abstract Organic heterostructures (OHTs) with the desired geometry organization on micro/nanoscale have undergone rapid progress in nanoscience and nanotechnology. However, it is a significant challenge to elucidate the epitaxial-growth process for various OHTs composed of organic units with a lattice mismatching ratio of > 3%, which is unimaginable for inorganic heterostructures. Herein, we have demonstrated a vivid visualization of the morphology evolution of epitaxial-growth based on a doped interfacial-layer, which facilitates the comprehensive understanding of the hierarchical self-assembly of core-shell OHT with precise spatial configuration. Significantly, the barcoded OHT with periodic shells obviously illustrate the shell epitaxial-growth from tips to center parts along the seeded rods for forming the core-shell OHT. Furthermore, the diameter, length, and number of periodic shells were modulated by finely tuning the stoichiometric ratio, crystalline time, and temperature, respectively. This epitaxial-growth process could be generalized to organic systems with facile chemical/structural compatibility for forming the desired OHTs.

Abstract Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

The cytochrome P450 enzyme is one of the largest protein families identified in cuticle biosynthesis, plant growth, development, and stress response. In the present study, 28 members of the MdCYP86A family were identified in apple (Malus × domestica Borkh.). Chromosomal localization analysis found that 28 genes were distributed on 13 chromosomes in apple. Phylogenetic and conserved motifs analysis showed that MdCYP86As in apple is evolutionarily most closely related to Arabidopsis thaliana. Each gene contains a cytochrome P450 domain, suggesting that MdCYP86As are highly conserved during the evolution of the species. Cis-acting element analysis of the promoter identified various elements associated with stress response. MdCYP86A21 was cloned in the apple genome to investigate the function of MdCYP86A family genes. MdCYP86A21 responded to abiotic stress, including PEG, NaCl, and ABA. The tissue-specific expression patterns revealed that the highest expression tissue was in flower by real-time quantitative reverse transcription (RT-qPCR). Subcellular localization showed that MdCYP86A21 was localized in the endoplasmic reticulum. Further, the function of MdCYP86A21 to enhance the resistance to PEG and NaCl stress in apple calli was verified. These results contribute to further study on the function of MdCYP86As and provide a molecular basis for the study of apple stress tolerance.

Abstract Limited endoscopic sphincterotomy (EST) combined with endoscopic papillary balloon dilation (EPBD) is widely used. However, the optimal duration of small balloon dilation in choledocholithiasis remains controversial. We aimed to determine the optimal duration for 10 mm diameter balloon dilation after limited EST in choledocholithiasis. In this randomized controlled clinical trial, 320 patients were randomly assigned to receive small balloon dilation (10 mm in diameter) for 1 min (n = 160) or 3 min (n = 160) after deep bile duct cannulation. No significant difference in success rate of stone extraction between the two groups was observed. The incidence of post-ERCP pancreatitis (PEP) was higher in the 1 min group (10.6%) than in the 3 min group (4.4%) (P = 0.034). The logistic regression analysis showed that guidewire into the pancreatic duct, cannulation time > 5 min and 1 min balloon dilation were independent risk factors for PEP. There were no significant differences in other post-ERCP adverse events such as acute cholangitis, bleeding, perforation, etc. between the two groups. In conclusion, 3 min in duration was determined to be the optimal dilation condition for the removal of common bile duct stones.

Plants encounter numerous adversities during growth, necessitating the identification of common stress activators to bolster their resistance. However, the current understanding of these activators’ mechanisms remains limited. This study identified three anti-stress activators applicable to apple trees, all of which elevate plant proline content to enhance resistance against various adversities. The results showed that the application of these sugar substitutes increased apple proline content by two to three times compared to the untreated group. Even at a lower concentration, these activators triggered plant stress resistance without compromising apple fruit quality. Therefore, these three sugar substitutes can be exogenously sprayed on apple trees to augment proline content and fortify stress resistance. Given their effectiveness and low production cost, these activators possess significant application value. Since they have been widely used in the food industry, they hold potential for broader application in plants, fostering apple industry development.

IntroductionObesity is a multi-factorial disease frequently associated with poor nutritional habits and linked to many detrimental health outcomes. Individuals with obesity are more likely to have increased levels of persistent inflammatory and metabolic dysregulation. The goal of this study was to compare four dietary patterns differentiated by macronutrient content in a postmenopausal model. Dietary patterns were high carbohydrate (HC), high fat (HF), high carbohydrate plus high fat (HCHF), and high protein (HP) with higher fiber.MethodsChanges in body weight and glucose levels were measured in female, ovariectomized C57BL/6 mice after 15 weeks of feeding. One group of five mice fed the HCHF diet was crossed over to the HP diet on day 84, modeling a 21-day intervention. In a follow-up study comparing the HCHF versus HP dietary patterns, systemic changes in inflammation, using an 80-cytokine array and metabolism, by untargeted liquid chromatography-mass spectrometry (LCMS)-based metabolomics were evaluated.ResultsOnly the HF and HCHF diets resulted in obesity, shown by significant differences in body weights compared to the HP diet. Body weight gains during the two-diet follow-up study were consistent with the four-diet study. On Day 105 of the 4-diet study, glucose levels were significantly lower for mice fed the HP diet than for those fed the HC and HF diets. Mice switched from the HCHF to the HP diet lost an average of 3.7 grams by the end of the 21-day intervention, but this corresponded with decreased food consumption. The HCHF pattern resulted in dramatic inflammatory dysregulation, as all 80 cytokines were elevated significantly in the livers of these mice after 15 weeks of HCHF diet exposure. Comparatively, only 32 markers changed significantly on the HP diet (24 up, 8 down). Metabolic perturbations in several endogenous biological pathways were also observed based on macronutrient differences and revealed dysfunction in several nutritionally relevant biosynthetic pathways.ConclusionOverall, the HCHF diet promoted detrimental impacts and changes linked to several diseases, including arthritis or breast neoplasms. Identification of dietary pattern-specific impacts in this model provides a means to monitor the effects of disease risk and test interventions to prevent poor health outcomes through nutritional modification.

BackgroundThe association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson’s disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients.MethodsIn this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson’s Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models.ResultsWe identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results.ConclusionThe current study found a significant dose–response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Angelica dahurica is a kind of Chinese traditional herbs with economic and ornament value, widely distributed in China. Despite its significance, there have been limited comprehensive investigations on the genome of A. dahurica, particularly regarding mitochondrial genomes. To investigate the conversion between mitochondrial genome and chloroplast genome, a complete and circular mitochondrial genome was assembled using Oxford Nanopore Technologies (ONT) long reads. The mitochondrial genome of A. dahurica had a length of 228,315 base pairs (bp) with 45.06% GC content. The mitochondrial genome encodes 56 genes, including 34 protein-coding genes, 19 tRNA genes and 3 rRNA genes. Moreover, we discovered that 9 homologous large fragments between chloroplast genome and mitochondrial genome based on sequence similarity. This is the first report for A. dahurica mitochondrial genome, which could provide an insight for communication between plastid genome, and also give a reference genome for medicinal plants within the Angelica family.

Abstract. Patients with chronic liver diseases (CLDs) have high hospitalization and mortality rates when combined with severe coronavirus disease 2019 (COVID-19) because of defects in humoral and cellular immunity, known as immune dysfunction. COVID-19 vaccines effectively reduce the risk of severe illness and mortality caused by the virus. Several studies have confirmed the safety and efficacy of the COVID-19 vaccine in patients with CLD, and the existing expert consensus recommends that patients with stable CLD be prioritized for the COVID-19 vaccine. In addition, clinical trials are ongoing to determine the optimal strategy for patients with CLD to receive the COVID-19 vaccine. In this study, we review the progress of research on the safety and efficacy of COVID-19 vaccination in patients with CLD, aiming to provide better recommendations for the vaccination in this population.

During the initial casting stage of the IF steel, the cleanliness of the first slab deteriorates. Steel plants treat the initial casting slabs as waste or demoting products. Moreover, the cleanliness deterioration of initial casting slabs leads to unstable quality and low product yield. In the present study, to investigate the cleanliness of continuous casting slabs and the optimization measures during the initial casting stage of the IF steel, the cleanliness of the initial casting slabs is evaluated by field sampling and experimental analysis. Moreover, the effect of the casting speed rising method on the cleanliness of the IF steel slab during the initial casting stage is investigated. Additionally, numerical simulations are conducted to reveal the level of fluctuations of the molten steel in the mold during the initial casting stage. The results show that the variations in T[O], [N], and the content of microinclusions in the slab decrease obviously along the casting direction. The contents of T[O] and [N] in the slab reach the normal slab level of 6 m (approximately 13×10−6) and 7 m (approximately 19×10−6) away from the dummy bar head, respectively. Nevertheless, the effects of the casting speed rising method on the contents of T[O], [N], and microinclusions in the initial casting slabs are inapparent during the open casting process. For the three conditions of open casting (different casting speed rising methods), the contents of the macroinclusions in the slab reach the normal slab level of around 2 m (approximately 2 mg/10 kg) away from the dummy bar head, respectively. Subsequently, the fluctuation of the macroinclusion content can be determined. Furthermore, under the condition of “quick-slow” casting speed rising, the fluctuation can be quickly alleviated, and the macroinclusion content normalizes. Numerical simulations reveal that the variations in the fluctuation level of the molten steel at different positions (near the nozzle, a quarter of the width, and near the narrow face) in the mold during the initial casting stage of the three casting speed rising modes are similar. First, the fluctuation level is extremely intense. Then, the fluctuation level gradually weakens for some time. Finally, the fluctuation level of the molten steel at different positions in the mold stabilizes. Additionally, the numerical simulation results reveal that the slab cleanliness can quickly normalize (430 s after initial casting and about 5 m away from the dummy bar head) under the “quick-slow” casting speed rising mode during the initial casting stage.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Abstract Erlotinib, an EGFR tyrosine kinase inhibitor, is used for treating patients with cancer exhibiting EGFR overexpression or mutation. However, the response rate of erlotinib is low among patients with gastric cancer (GC). The findings of this study illustrated that the overexpression of bromodomain PHD finger transcription factor (BPTF) is partially responsible for erlotinib resistance in GC, and the combination of the BPTF inhibitor AU‐1 with erlotinib synergistically inhibited tumor growth both in vivo and in vitro. AU‐1 inhibited the epigenetic function of BPTF and decreased the transcriptional activity of c‐MYC on PLCG1 by attenuating chromosome accessibility of the PLCG1 promoter region, thus decreasing the expression of p‐PLCG1 and p‐Erk and eventually improving the sensitivity of GC cells to erlotinib. In patient‐derived xenograft (PDX) models, AU‐1 monotherapy exhibited remarkable tumor‐inhibiting activity and is synergistic anti‐tumor effects when combined with erlotinib. Altogether, the findings illustrate that BPTF affects the responsiveness of GC to erlotinib by epigenetically regulating the c‐MYC/PLCG1/pErk axis, and the combination of BPTF inhibitors and erlotinib is a viable therapeutic approach for GC.

A number of enzymes and transcription factors involved in cuticular wax biosynthesis have been identified in numerous plant species. The pathway of wax biosynthesis is relatively definite. The molecular basis of cuticular wax deposition is still unclear, especially the transport mechanism of cuticular wax from endoplasmic reticulum (ER) to the cell wall. It has been found that the ABCG transporter family is involved in the wax export process in some model plants. However, whether ABCG transporters participate in wax transport in apple is unknown. In this study, MdABCG25, encoding an ABCG transporter, was isolated from apple (Malus domestica Brokh.). MdABCG25, containing an AAA domain and an ABC2_membrane domain, is highly expressed in apple pericarp and induced by drought, salt and ABA conditions. The heterologous expression of MdABCG25 in Arabidopsis leads to an increasing cuticular wax accumulation of stems and leaves. The epidermal permeability, water loss rate and chlorophyll extraction rate of MdABCG25 transgenic Arabidopsis were decreased. The expression of MdABCG25 improved the drought and salt tolerance of apple calli and Arabidopsis.

Cuticular wax covers the surface of the apple epidermis and plays an important role in water loss and pathogen resistance. However, little is known about wax biosynthesis during apple fruit development. In this study, the morphological structure and chemical composition of wax and the transcription patterns of wax-related genes were investigated in the 'Red Delicious' and 'Golden Delicious' cultivars. The results showed that accumulation of the waxy layer was synchronized with enlargement and maturation of fruit. The crystal structure, major chemical components (very long chain fatty acids and triterpenes) of wax and the expression levels of wax-related genes varied significantly 90 days after flowering (DAF), indicating that the critical period for biosynthesis of cuticular wax was about 90 DAF. This finding is valuable for further study of the regulatory mechanism of wax biosynthesis at both the molecular and physiological levels.

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility. [ABSTRACT FROM AUTHOR]

Keteleeria davidiana (Bertrand) Beissner 1891 (Pinaceae) is a rare tertiary relict plant endemic to China. However, since the main morphological characteristics used for identifying K. davidiana are variable, some taxonomic treatments within the species are still controversial. Here a complete chloroplast genome of K. davidiana representing a special genotype was assembled, which could provide more information for the taxonomic study of this species. The assembled genome was 117,642 bp in length with a large single-copy (LSC) region (74,825 bp), a small single-copy (SSC) region (40,247 bp), and two incomplete inverted repeats (IRs) regions (1285 bp each). In total, 118 genes were predicted, including 4 rRNAs, 34 tRNAs, and 80 protein-coding genes. The overall GC content of the assembled genome was 38.5%. Phylogenetic analysis showed that different accessions of K. davidiana formed a clade with relatively low support (bootstrap value = 71), which indicated a high level of sequences variation within the species.

Gardenia jasminoides Ellis is a traditional aromatic and medicinal plant in China. Here, the complete chloroplast genome of a wild-type gardenia adapted to island climate was assembled. The assembled genome was 155,247 bp in length, with four typical regions, i.e., a large single-copy (LSC) region (85,414 bp), a small single-copy (SSC) region (18,235 bp) and two inverted repeats (IRs) regions (25,799 bp each). In total, 138 genes were predicted, including 90 protein-coding genes, 40 tRNA genes and eight rRNA genes. The overall GC content of the chloroplast genome was 37.5%. The chloroplast genome would provide more information for the phylogeography and phylogeny study of G. jasminoides.