A network pharmacology integrated serum pharmacochemistry strategy for uncovering efficacy of YXC on hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The YangzhengXiaoji capsule (YXC) has a wide range of applications as effective traditional Chinese medicine (TCM) preparation for hepatocellular carcinoma (HCC) in China. However, the potential bioactive components and the mechanisms are yet unclear. AIM OF THE STUDY: The treatment mechanism of YXC on HCC using a network pharmacology integrated serum pharmacochemistry strategy to investigate associated targets and pathways. MATERIALS AND METHODS: We utilised HPLC-Q-TOF-MS/MS technology to identify components of the serum samples from both the model group and the YXC (H) group serum, which were collected from nude mice with orthotopic liver tumours. Following this, we conducted compound-target prediction and identified the overlap between the target genes in the YXC group and the oncogenes associated with HCC. The anticancer mechanisms of YXC were investigated by creating a compound-target-pathway network using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis. The anticancer efficacy was evaluated in vitro and in vivo. Also, potential predictive targets and pathways associated with YXC in HCC treatment were assessed by western blotting. RESULTS: The YXC (H) serum had 47 bioactive compounds compared to other models, and identified 173 specific target genes. Using the compound-target-disease network, 141 possible target genes were identified. The KEGG pathway analysis revealed vital enrichment of pathways associated with HCC, including regulating Oncology related pathways of inflammation, immunity, apoptosis, and necrosis biological processes. YXC significantly inhibited HCC cell growth in vitro and in vivo. After YXC treatment, western blotting detected alterations in the p53/Bcl-2/Bax/Caspase-3 and PI3K/Akt pathways. CONCLUSIONS: YXC can inhibit HCC development and advancement by a variety of components, targets and pathways, especially apoptosis-induction.

The Fatal Defects in Cast Al-Si Alloys Due to Sn Addition.

Cast defects are common in cast alloys and they are difficult to eliminate without deformation. They strongly degrade the mechanical properties of cast alloys. The addition of some elements can affect the number of cast defects. In this work, the deleterious effect of Sn addition on the mechanical properties of Al-Si alloys has been investigated via 3D-computed tomography, SEM and TEM. Amorphous Sn oxides were found near the alumina film or formed enclosures with alumina film. The melt containing high Sn content was trapped by enclosures, causing more shrinkage pores during solidification. Cracks likely initiated and expanded along these pores and brittle amorphous Sn oxides, deteriorating the mechanical properties. This work suggests not adding Sn to various Al alloys when used in a cast state.

Sex differences in major adverse cardiovascular and cerebrovascular event risk among central retinal artery occlusion patients.

To estimate the association between central retinal artery occlusion (CRAO) and major adverse cardiovascular and cerebrovascular events (MACCE), including their clinical characteristics, blood markers, and the contribution of CRAO to MACCE, as well as to assess any sex differences. This retrospective cohort study included continuous new-onset CRAO patients and 1:4 controls during the same period. Correlations of CRAO with the incidence of MACCE during follow-up and the sex-related differences were studied. One hundred and twenty-four CRAO patients and four hundred and ninety-six controls were enrolled. Neutrophil-to-lymphocyte ratio (NLR, P = 0.014) and high-sensitivity C-reactive protein (hs-CRP, P = 0.038) were tended to be higher in CRAO patients. After the follow-up period, 78 patients experienced MACCE. Multivariate Cox regression analysis showed that CRAO was a predictor of the occurrence of MACCE (HR 2.321, 95% CI 1.439-3.744, P = 0.001). Sex subgroups indicated that age, diabetes, current smoking, CRAO, NLR and hs-CRP increased the risk factor of MACCE in males (All P < 0.05) and CRAO, NLR, low-density lipoprotein cholesterol (LDL-C) and hs-CRP were independent influencing factors for females (All P < 0.05). New-onset CRAO significantly increases the probability of MACCE and is associated with a poor prognosis. The sex-related differences suggested that effective prevention of the occurrence of MACCE in high-risk patients requires that attention be given to individualized risk factors corresponding to sexes.

Magnetic resonance imaging findings of pulmonary sclerosing pneumocytoma: a case report and literature review.

Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare lung tumor that is mostly isolated and commonly reported among middle-aged East Asian women. Recently, Immunohistochemistry (IHC) analysis has suggested that PSP is of primitive epithelial origin, most likely derived from type II alveolar air cells. Patients with PSP are generally asymptomatic and usually detected for other unrelated reasons during routine imaging. Several studies have already investigated the computed tomography (CT) features of PSP and their correlation with pathology. Magnetic resonance imaging (MRI) is a radiation-free imaging technique with important diagnostic value for specific pulmonary nodules. However, very few case reports or studies focus on the MRI findings of PSP. Case report: We reported a case of an asymptomatic 56-year-old female with a solitary, well-defined soft-tissue mass in the lower lobe of the left lung. The mass showed iso-to-high signal intensity (SI) than muscle on T1-weighted image (T1WI) and T2-weighted image (T2WI) and a much higher SI on fat-suppressed T2WI, diffusion-weighted image, and apparent diffusion coefficient image. Contrast-enhanced fat-suppressed T1WI revealed noticeable inhomogeneous progressive enhancement throughout the mass. The mass revealed early enhancement without a significant peak, followed by a plateau pattern on dynamic contrast-enhanced MRI images. The patient underwent left basal segmentectomy via thoracoscopic surgery. Histopathology and IHC results of the surgical specimen confirmed that it was a PSP. We concluded that the MRI findings of PSP might adequately reflect the different components within the tumor and aid clinicians in preoperative diagnosis and assessment. To the best of our knowledge, this is the most comprehensive case report on the MRI findings of PSP. Conclusion: The MRI findings of PSP correspond to its histopathological features. Here, we present a case of PSP with the most comprehensive MRI findings, emphasizing the importance of multiple-sequence MRI in diagnosing PSP.

Microstructure characterization of different types of chlamydospores in Arthrobotrys flagrans.

The morphological and structural differences of different types of chlamydospore of Arthrobotrys flagrans, a nematophagous fungus, were studied under light microscope and electron microscope to provide a reference for the biological control of parasitic nematodiasis. In this study, A. flagrans isolate F088 dormant chlamydospore and nondormant chlamydospore were selected as the research objects. The structural differences of these spores were observed by optical microscopy through lactol cotton blue, Trypan blue, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. FunXite -1, 4',6-diamidino-2-phenylindole, and calcofluor white staining were used to observe the metabolic activity, cell wall, and nucleus differences of the two types of spores under fluorescence microscope. Ultrastructure of the two kinds of spores was observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). Since lacto phenol cotton blue, trypan blue staining cannot distinguish dormant spores from dead spores, MTT assay was performed. Fluorescence microscopy observation showed that the cytoplasmic metabolic activity of nondormant spores was stronger than that of dormant spores. The nucleus of dormant spores was bright blue, and their fluorescence was stronger than that of nondormant spores. The cell wall of nondormant spores produced stronger yellow-green fluorescence than that of dormant spores. Ultrastructural observation showed that there were globular protuberances on the surface of the two types of spores but with no significant difference between them. The inner wall of dormant spore possesses a thick zona pellucida with high electron density which was significantly thicker than that of nondormant spores, and their cytoplasm is also changed. In this study, the microstructure characteristics of dormant and nondormant chlamydospores of A. flagrans fungi were preliminarily clarified, suggesting that the state of cell wall and intracellular materials were changed after spores entered to dormancy.

[Occurrence and Fate of Steroid Hormones in Sewage Treatment Plants].

Sewage treatment plants (STPs) are one of the crucial barriers for the environmental emission of steroid hormones. Insights into the occurrence and fate of different categories of steroid hormones in STPs could provide theoretical support for improving steroid removal by STPs. The present study investigated 22 steroid hormones in each treatment process of two STPs located in Wuxi via eight monthly sampling campaigns and compared the efficacy of Anaerobic-Anoxic-Aerobic (A2/O) and reversed A2/O treatments. The results showed that the total steroid concentrations in the influent and effluent were 27.7-256.8 ng·L-1 and 5.7-211.0 ng·L-1, respectively, and 36.3-123.6 ng·g-1 in the excess sludge. Androsterone, androstenedione, estrone, estriol, and progesterone were the main species detected in the STPs. The concentrations of most steroids increased with the rise of rainfall and temperature, whereas the removal rates were not significantly different between winter and summer. Secondary and tertiary treatment processes showed better performance in steroid removal compared with that in the primary treatment; however, reversed A2/O did not show advantages over traditional A2/O. The organic-normalized partition coefficients (lg Koc) of steroids ranged between 2 and 4.5. The values of lg Koc in STP A were slightly greater than those in STP B, indicating that the partition behavior of steroids may influence their treatment efficacies.

Development and Validation of Frailty and Malnutrition Knowledge Assessment Scale for Community-Dwelling Older Adults.

There is a lack of reliable tools to assess the knowledge of frailty and malnutrition in community-dwelling older adults. To develop and validate reliable frailty and malnutrition knowledge assessment scales for this population. The two scales were developed and validated through 5 phases. Phase 1: the item pools were constructed through a literature review and research panel based on the Symptom Interpretation Model. Phase 2: the expert consultation was performed to select the items. Phase 3: a pilot survey was conducted to assess the clarity of the items and to further revise the scales. Phase 4: 242 older adults were surveyed to finalize the items. Phase 5: 241 older adults were surveyed to test the psychometric properties. The two scales both comprise three dimensions (symptoms, risk factors, and management strategies) and 11 items. They had good construct validity, with all indicators of correlation analysis and confirmatory factor analysis meeting their specific criteria. The reliability of the frailty and malnutrition knowledge assessment scales was good, with composite reliability coefficients all > 0.60; Cronbach's alpha being 0.81 and 0.83, and the Spearman-Brown coefficient being 0.74 and 0.80, respectively. Their acceptability was good, with both having a completion rate of 92.18% and an average completion time of 3 minutes. The two scales are reliable tools to assess the knowledge of frailty and malnutrition among community-dwelling older adults, especially for large-scale surveys. They can help identify knowledge gaps in older adults and provide a basis for developing targeted educational interventions.

Anti-Allergic and Anti-inflammatory Effects of Bakuchiol on Ovalbumin-Induced Allergic Rhinitis in Mice.

Allergic rhinitis (AR) is a prevalent inflammatory disease primarily affecting the nasal mucosa and is caused by allergies. The common symptoms of AR include rhinorrhea, sneezing, itchy nose, congestion, teary eyes, and nasal rubbings. The present study assessed the beneficial properties of bakuchiol on OVA-induced AR in mice via the regulation of inflammatory responses. AR was induced by injecting (i.p.) OVA (50 µg) and aluminum hydroxide (1 mg) into mice at various time intervals. The bakuchiol treatment was done at dosages of 10 and 20 mg/kg with dexamethasone (2.5 mg/kg) as a positive control. The body weight and nasal symptoms were measured on the day of the last OVA challenge. For in vitro tests, mouse splenocytes were isolated, sensitized with 20 µL OVA, and then treated with 10 µM bakuchiol. The levels of pro-inflammatory cytokines, immunoglobulins, histamine, leukotriene C4 (LTC-4), and prostaglandin D2 (PGD2) were assayed using the corresponding assay kits. The assay kits were also used to analyze the status of oxidative stress markers. The Th1/Th2 cell proportion was assessed using flow cytometry. The bakuchiol (10 and 20 mg/kg) treatment reduced the nasal symptoms in AR mice. Bakuchiol decreased the levels of IL-4, IL-5, IL-13, Igs (IgE and IgG1), histamine, IL-10, IL-33, and TNF-α in AR mice. Bakuchiol also reduced PGDA and LTC-4 levels in the NLF of AR mice. The ROS and MDA levels were decreased, whereas boosted SOD activity was observed in the bakuchiol-treated AR mice. The eosinophil count was decreased in the nasal tissues of bakuchiol-treated AR mice. Bakuchiol also influenced the Th1 and Th2 cell proportions in AR mice. The present findings suggest that bakuchiol is effective against OVA-mediated allergic and inflammatory responses in AR mice through its strong anti-inflammatory properties.

Volatile Organic Compounds Emitted by the Biocontrol Agent Pythium oligandrum Contribute to Ginger Plant Growth and Disease Resistance.

The oomycete Pythium oligandrum is a potential biocontrol agent to control a wide range of fungal and oomycete-caused diseases, such as Pythium myriotylum-caused rhizome rot in ginger, leading to reduced yields and compromised quality. Previously, P. oligandrum has been studied for its plant growth-promoting potential by auxin production and induction of disease resistance by elicitors such as oligandrin. Volatile organic compounds (VOCs) play beneficial roles in sustainable agriculture by enhancing plant growth and resistance. We investigated the contribution of P. oligandrum-produced VOCs on plant growth and disease suppression by initially using Nicotiana benthamiana plants for screening. P. oligandrum VOCs significantly enhanced tobacco seedling and plant biomass contents. Screening of the individual VOCs showed that 3-octanone and hexadecane promoted the growth of tobacco seedlings. The total VOCs from P. oligandrum also enhanced the shoot and root growth of ginger plants. Transcriptomic analysis showed a higher expression of genes related to plant growth hormones and stress responses in the leaves of ginger plants exposed to P. oligandrum VOCs. The concentrations of plant growth hormones such as auxin, zeatin, and gibberellic acid were higher in the leaves of ginger plants exposed to P. oligandrum VOCs. In a ginger disease biocontrol assay, the VOC-exposed ginger plants infected with P. myriotylum had lower levels of disease severity. We conclude that this study contributes to understanding the growth-promoting mechanisms of P. oligandrum on ginger and tobacco, priming of ginger plants against various stresses, and the mechanisms of action of P. oligandrum as a biocontrol agent. IMPORTANCE Plant growth promotion plays a vital role in enhancing production of agricultural crops, and Pythium oligandrum is known for its plant growth-promoting potential through production of auxins and induction of resistance by elicitors. This study highlights the significance of P. oligandrum-produced VOCs in plant growth promotion and disease resistance. Transcriptomic analyses of leaves of ginger plants exposed to P. oligandrum VOCs revealed the upregulation of genes involved in plant growth hormone signaling and stress responses. Moreover, the concentration of growth hormones significantly increased in P. oligandrum VOC-exposed ginger plants. Additionally, the disease severity was reduced in P. myriotylum-infected ginger plants exposed to P. oligandrum VOCs. In ginger, P. myriotylum-caused rhizome rot disease results in severe losses, and biocontrol has a role as part of an integrated pest management strategy for rhizome rot disease. Overall, growth enhancement and disease reduction in plants exposed to P. oligandrum-produced VOCs contribute to its role as a biocontrol agent.

The CAP superfamily protein PsCAP1 secreted by Phytophthora triggers immune responses in Nicotiana benthamiana through a leucine-rich repeat receptor-like protein.

The role of cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 (CAP) superfamily proteins in the innate immune responses of mammals is well characterized. However, the biological function of CAP superfamily proteins in plant-microbe interactions is poorly understood. We used proteomics and transcriptome analyses to dissect the apoplastic effectors secreted by the oomycete Phytophthora sojae during early infection of soybean leaves. By transiently expressing these effectors in Nicotiana benthamiana, we identified PsCAP1, a novel type of secreted CAP protein that triggers immune responses in multiple solanaceous plants including N. benthamiana. This secreted CAP protein is conserved among oomycetes, and multiple PsCAP1 homologs can be recognized by N. benthamiana. PsCAP1-triggered immune responses depend on the N-terminal immunogenic fragment (aa 27-151). Pretreatment of N. benthamiana with PsCAP1 or the immunogenic fragment increases plant resistance against Phytophthora. The recognition of PsCAP1 and different homologs requires the leucine-rich repeat receptor-like protein RCAP1, which associates with two central receptor-like kinases BRI1-associated receptor kinase 1 (BAK1) and suppressor of BIR1-1 (SOBIR1) in planta. These findings suggest that the CAP-type apoplastic effectors act as an important player in plant-microbe interactions that can be perceived by plant membrane-localized receptor to activate plant resistance.

Comparison of different risk stratifications for gastric cancer and establishing a simplified risk-scoring model based on the Kyoto classification.

BACKGROUND AND AIM: The study aims to assess the value of different risk stratifications in diagnosing early gastric cancer (GC) and explore risk factors based on Kyoto gastritis classification. METHODS: This study was a single-centered cross-sectional study; all epidemiological data and endoscopic findings were obtained prospectively. To evaluate the proportion of GC in each risk stratification and to compare the diagnostic performance of different methods using the receiver operating characteristic curve, univariable and multivariable analyses were used to explore the correlation between endoscopic findings and GC. RESULTS: A total of 240 subjects were enrolled, and the diagnostic efficacy of the Kyoto Classification Score was similar to Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, and the accuracy was higher than that of the Japanese scoring system and OLGA stage. Moderate atrophy (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.52-8.16), severe atrophy (OR = 4.96, 95% CI: 1.75-14.04), map-like redness (OR = 9.89, 95% CI: 1.16-84.15), and xanthelasma (OR = 3.57, 95% CI: 1.15-11.15) were independent risk factors for GC. The simplified Kyoto classification (area under the receiver operating characteristic [AUROC] = 0.76, P = 0.58) based on multivariable analysis demonstrated favorable diagnostic value compared with traditional Kyoto classification score (AUROC = 0.74). CONCLUSIONS: This study confirms the value of the Kyoto classification score and the OLGIM stage in the risk stratification of GC. Simplified Kyoto classification is also promising in risk assessment of GC but still requires validation in the population.

Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis (AP) often leads to a high incidence of cardiac injury, posing significant challenges in the treatment of severe AP and contributing to increased mortality rates. Mesenchymal stem cells (MSCs) release bioactive molecules that participate in various inflammatory diseases. Similarly, extracellular vesicles (EVs) secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation. Recently, the therapeutic potential of MSCs-EVs in various inflammatory diseases, including sepsis and AP, has gained increasing recognition. Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited, several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases. Furthermore, clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases, wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs. Consequently, we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury. This paper aims to discuss this topic. However, additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury, as well as to ascertain their safety and efficacy.

Antimicrobial mechanisms of ZnO nanoparticles to phytopathogen Pseudomonas syringae: Damage of cell envelope, suppression of metabolism, biofilm and motility, and stimulation of stomatal immunity on host plant.

Nanoparticles have recently been employed as a new strategy to act as bactericides in agricultural applications. However, the effects and mechanisms of foliar deposition of nanoparticles on bacterial pathogens, plant physiology and particularly plant immunity have not been sufficiently understood. Here, we investigated the effects and mechanisms of ZnO NPs in controlling of tobacco wildfire caused by Pseudomonas syringae pv. tabaci, through the comprehensive analysis of biological changes of both bacteria and plants. The global gene expression changes of Pseudomonas syringae pv. tabaci supported that the functions of "protein secretion", "membrane part", "signal transducer activity", "locomotion", "chemotaxis" and "taxis" in bacteria, as well as the metabolic pathways of "bacterial chemotaxis", "two-component system", "biofilm formation", "ABC transporters" and "valine, leucine and isoleucine degradation" were significantly down-regulated by ZnO NPs. Correspondingly, we reconfirmed that the cell envelope structure, biofilm and motility of Pseudomonas syringae pv. tabaci were directly disrupted or suppressed by ZnO NPs. Different from completely killing Pseudomonas syringae pv. tabaci, ZnO NPs (0.5 mg/mL) potentially improved plant growth and immunity through enzymatic activity and global molecular response analysis. Furthermore, the changes of gene expression in ABA signaling pathway, ABA concentration and stomatal aperture all supported that ZnO NPs can specifically stimulate stomatal immunity, which is important to defend bacterial infection. Taken together, we proposed that both the inhibition or damage of motility, biofilm, metabolisms, virulence and cell envelope on P. syringae pv. tabaci, and the activation of the stomatal immunity formed two-layered antibacterial mechanisms of ZnO NPs on phytopathogenic bacteria.

CIRCTDRD9 CONTRIBUTES TO SEPSIS-INDUCED ACUTE LUNG INJURY BY ENHANCING THE EXPRESSION OF RAB10 VIA DIRECTLY BINDING TO MIR-223-3P.

ABSTRACT: Background: The dysregulation of circular RNAs (circRNAs) is involved in various human diseases, including sepsis-induced acute lung injury (ALI). We aimed to investigate the role of circTDRD9 in the development of sepsis-induced ALI. Methods: Cell models of sepsis-induced ALI were established by treating A549 cells with LPS. The expression of circTDRD9, miR-223-3p, and RAB10 mRNA was measured by quantitative real-time PCR (qPCR). The levels of inflammatory factors were measured by ELISA. Oxidative stress-related indicators were monitored by using commercial detection kits. The expression of fibrosis-related proteins was detected by Western blot assay. Cell proliferation was assessed by EdU assay. The predicted binding relationship between miR-223-3p and circTDRD9 or RAB10 was verified by dual-luciferase reporter assay, RIP assay or pull-down assay. Results: CircTDRD9 was highly expressed in LPS-treated A549 cells. CircTDRD9 downregulation prevented LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells, whereas these effects were reversed by the inhibition of miR-223-3p, a target of circTDRD9. In addition, RAB10 was verified as a target of miR-223-3p, and RAB10 overexpression recovered LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells that were ameliorated by miR-223-3p restoration. Importantly, circTDRD9 positively regulated RAB10 expression by binding to miR-223-3p. Conclusion: CircTDRD9 overexpression was closely associated with LPS-induced ALI. CircTDRD9 contributed to LPS-induced ALI partly by upregulating RAB10 via binding to miR-223-3p.

Composite g-C3 N4 @ZnO NP electrostatic self-assembly: enhanced ROS as a key factor for high-efficiency control of tobacco wildfire disease.

BACKGROUND: The utilization of non-metallic inorganic nanomaterials for antimicrobial photocatalytic technology has emerged as a promising approach to combat drug-resistant bacteria. Recently, g-C3 N4 nanosheets have attracted significant attention due to their exceptional stability, degradability, low cost, and remarkable antibacterial properties. In this study, a facile electrostatic self-assembly approach was utilized to functionalize ZnO nanoparticles with g-C3 N4 nanosheets, resulting in the formation of g-C3 N4 @ZnO nanoparticle composites. RESULTS: The Z-shaped heterojunction architecture of these composites facilitates efficient separation of photogenerated electron-hole pairs and enhances visible light catalytic performance. Moreover, the formation of the g-C3 N4 @ZnO heterostructure showed a higher photocatalytic capacity and the generation of reactive oxygen species (ROS) than g-C3 N4 nanosheets. The photocatalytic antibacterial mechanisms of g-C3 N4 @ZnO at the transcriptomic level primarily involve disrupting bacterial membrane synthesis and inhibiting motility and energy metabolism. Therefore, the antibacterial mechanism of g-C3 N4 @ZnO can be attributed to a combination of physical membrane damage, chemical damage (ROS enhancement) and inhibition of chemotaxis, biofilm formation and flagellar motility. CONCLUSION: These findings collectively provide novel high potential and insights into the practical application of photocatalysts in plant disease management. © 2023 Society of Chemical Industry.

Study on the association of the microstructure and bone metabolism in the osteoporotic femoral head.

BACKGROUND: We compared the bone microstructure and metabolism of the femoral heads in patients with osteoporosis (OP) and non-OP patients to investigate the pathologic mechanism of OP and guide clinical treatment. METHODS AND RESULTS: From January 2020 to June 2021, we obtained femoral head samples from 30 patients undergoing hip replacement due to femoral neck fracture. All patients were women aged approximately 67 to 80 years (mean age, 74 years). According to the dual-energy X-ray results, the femoral head samples were divided into the OP (T< - 2.5) and non-OP (T > - 1.5) groups. Microcomputed tomography scanning, bone metrology analysis, hematoxylin and eosin staining, and Masson's trichrome staining were used to compare the local bone trabecular microstructure changes. Quantitative reverse transcription PCR was performed to identify changes in the osteogenesis-related genes and the osteoclast-related genes in specific regions to reflect osteogenic and osteoclastic activities. Femoral heads with OP showed significant changes in the local bone microstructure. Bone density, bone volume fraction, and the number and thickness of the bone trabeculae decreased. Local bone metabolism was imbalanced in the areas with microstructural changes in femoral heads with OP, with increased osteoclast activity and decreased osteoblast activity. CONCLUSIONS: Deterioration of bone microstructure is closely related to abnormal bone metabolism associated with the activity of osteoblasts and osteoclasts in osteoporotic femoral heads. Promoting bone formation by improving local bone metabolism, enhancing osteogenic activity and inhibiting osteoclast activity may be a promising way of preventing local OP and osteoporotic fractures.

Deciphering genetic basis of developmental and agronomic traits by integrating high-throughput optical phenotyping and genome-wide association studies in wheat.

Dissecting the genetic basis of complex traits such as dynamic growth and yield potential is a major challenge in crops. Monitoring the growth throughout growing season in a large wheat population to uncover the temporal genetic controls for plant growth and yield-related traits has so far not been explored. In this study, a diverse wheat panel composed of 288 lines was monitored by a non-invasive and high-throughput phenotyping platform to collect growth traits from seedling to grain filling stage and their relationship with yield-related traits was further explored. Whole genome re-sequencing of the panel provided 12.64 million markers for a high-resolution genome-wide association analysis using 190 image-based traits and 17 agronomic traits. A total of 8327 marker-trait associations were detected and clustered into 1605 quantitative trait loci (QTLs) including a number of known genes or QTLs. We identified 277 pleiotropic QTLs controlling multiple traits at different growth stages which revealed temporal dynamics of QTLs action on plant development and yield production in wheat. A candidate gene related to plant growth that was detected by image traits was further validated. Particularly, our study demonstrated that the yield-related traits are largely predictable using models developed based on i-traits and provide possibility for high-throughput early selection, thus to accelerate breeding process. Our study explored the genetic architecture of growth and yield-related traits by combining high-throughput phenotyping and genotyping, which further unravelled the complex and stage-specific contributions of genetic loci to optimize growth and yield in wheat.

Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer.

BACKGROUND: The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. METHODS: The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39-0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31-0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1-2. CONCLUSIONS: Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

Interspecific variation and phylogenetic relationship between mangrove and non-mangrove species of a same family (Meliaceae)-insights from comparative analysis of complete chloroplast genome.

The mahogany family, Meliaceae, contains 58 genera with only one mangrove genus: Xylocarpus. Two of the three species of the genus Xylocarpus are true mangroves (X. granatum and X. moluccensis), and one is a non-mangrove (X. rumphii). In order to resolve the phylogenetic relationship between the mangrove and non-mangrove species, we sequenced chloroplast genomes of these Xylocarpus species along with two non-mangrove species of the Meliaceae family (Carapa guianensis and Swietenia macrophylla) and compared the genome features and variations across the five species. The five Meliaceae species shared 130 genes (85 protein-coding genes, 37 tRNA, and eight rRNA) with identical direction and order, with a few variations in genes and intergenic spacers. The repetitive sequences identified in the rpl22 gene region only occurred in Xylocarpus, while the repetitive sequences in accD were found in X. moluccensis and X. rumphii. The TrnH-GUG and rpl32 gene regions and four non-coding gene regions showed high variabilities between X. granatum and the two non-mangrove species (S. macrophylla and C. guianensis). In addition, among the Xylocarpus species, only two genes (accD and clpP) showed positive selection. Carapa guianensis and S. macrophylla owned unique RNA editing sites. The above genes played an important role in acclimation to different stress factors like heat, low temperature, high UV light, and high salinity. Phylogenetic analysis with 22 species in the order Sapindales supported previous studies, which revealed that the non-mangrove species X. rumphii is closer to X. moluccensis than X. granatum. Overall, our results provided important insights into the variation of genetic structure and adaptation mechanism at interspecific (three Xylocarpus species) and intergeneric (mangrove and non-mangrove genera) levels.