A damage constitutive model of layered slate under the action of triaxial compression and water environment erosion.

Based on the macroscopic structure control theory, The slate with a significant bedding plane is a composite rock mass composed of rock blocks containing microscopic defects, joint surface closure elements, and shear deformation elements. Considering the coupling damage effect of water erosion and triaxial compressive load on bedding structure plane, the transversely isotropic damage constitutive model of slate under triaxial compressive load is derived with the dip angle of bedding and confining pressure as the variable. Firstly, based on the statistical theory of continuous damage mechanics and the maximum tensile strain criterion, the transversely isotropic deformation constitutive model of rock block with micro-defects is given; Secondly, based on the phenomenological theory of closed deformation and shear-slip deformation mechanism of layered structural plane under the coupling action of water erosion and triaxial compression load, the calculation formula of axial deformation of layered structural plane under the coupling action is given; Finally, to verify the accuracy of the established constitutive model, triaxial compression tests are carried out to study the influence of dip angle and confining pressure on the macroscopic mechanical properties and mechanism of slate. The results show that: the established triaxial compression damage constitutive model of bedding slate can accurately describe the stress-strain relationship of bedding slate after water environment erosion. With the increase of bedding dip angle, the strength and deformation capacity of the bedding slate first decreases and then increases, showing a U-shaped distribution as a whole. There are three main types of failure: tension shear composite failure, shear slip failure, and splitting tension failure.

Non-invasive imaging for predicting labial salivary gland biopsy outcomes in patients with suspected primary Sjögren syndrome.

To identify the value of salivary gland ultrasound (SGUS) combined with magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) in predicting the results of labial salivary gland biopsy (LSGB) in patients with suspected primary Sjögren syndrome (pSS), and construct a nomogram model to predict LSGB results. A total of 181 patients who were admitted with suspected pSS from December 2018 to April 2023 were examined and divided into a training set (n = 120) and a validation set (n = 61). Baseline data of the two groups were examined, and the value of SGUS, MRI, and MRS in predicting LSGB was analyzed. Multivariate logistic analysis was used to screen for risk factors, and nomogram prediction models were constructed using these results. In the training set, the SGUS, MRI, and MRS scores of patients in the LSGB + group were higher than those in the LSGB - group (all P < 0.001). The positive prediction value (PPV) was 91% for an SGUS score of 3, and 82% for MRI and MRS scores of 2 or more. We developed a nomogram prediction model based on SGUS, MRI, and MRS data, and it had a concordance index (C-index) of 0.94. The Hosmer-Lemeshow test (χ2 = 3.17, P = 0.92) also indicated the nomogram prediction model had good accuracy and calibration for prediction of LSGB results. A nomogram model based on SGUS, MRI, and MRS results can help rheumatologists decide whether LSGB should be performed in patients with suspected pSS.

Molecular characterization of the cytochrome P450 enzyme CYP18A1 in Henosepilachna vigintioctopunctata.

In insects, the expression of 20E response genes that initiate metamorphosis is triggered by a pulse of 20-hydroxyecdysone (20E). The 20E pulse is generated through two processes: synthesis, which increases its level, and inactivation, which decreases its titer. CYP18A1 functions as an ecdysteroid 26-hydroxylase and plays a role in 20E removal in several representative insects. However, applying 20E degradation activity of CYP18A1 to other insects remains a significant challenge. In this study, we discovered high levels of Hvcyp18a1 during the larval and late pupal stages, particularly in the larval epidermis and fat body of Henosepilachna vigintioctopunctata, a damaging Coleopteran pest of potatoes. RNA interference (RNAi) targeting Hvcyp18a1 disrupted the pupation. Approximately 75% of the Hvcyp18a1 RNAi larvae experienced developmental arrest and remained as stunted prepupae. Subsequently, they gradually turned black and eventually died. Among the Hvcyp18a1-depleted animals that successfully pupated, around half became malformed pupae with swollen elytra and hindwings. The emerged adults from these deformed pupae appeared misshapen, with shriveled elytra and hindwings, and were wrapped in the pupal exuviae. Furthermore, RNAi of Hvcyp18a1 increased the expression of a 20E receptor gene (HvEcR) and four 20E response transcripts (HvE75, HvHR3, HvBrC, and HvαFTZ-F1), while decreased the transcription of HvßFTZ-F1. Our findings confirm the vital role of CYP18A1 in the pupation, potentially involved in the degradation of 20E in H. vigintioctopunctata.

Damage and reliability analysis of double-arch tunnel without a middle pilot tunnel under blast load.

In this study, a new type of multi-arch tunnel construction method is proposed. This effort is undertaken due to the many disadvantages of the traditional multi-arch tunnel construction method. Furthermore, this method omits the construction of a middle pilot tunnel, and it has the advantages of safety, high efficiency, and being economical. When using the method of continuous arch tunneling without a middle pilot tunnel, the blasting of the first tunnel and the following tunnel has a greater impact on the surrounding rock damage, as well as on the supporting structure of the same cross-section. Therefore, this study uses LS-DYNA finite element software to construct a three-dimensional numerical model. In addition, the perimeter rock damage law and mechanical response characteristics of the supporting structure in the same cross-section of the first tunnel, as well as the following tunnel after blasting without a middle pilot tunnel, are analyzed. At the same time, the results of the study are based on optimizing the blasting program, and these are then applied to the field. Through the results, it is found that, after blasting a continuous arch tunnel without a medial pilot tunnel, the surrounding rock damage in the arch cross-region of the double-arch tunnel (where the arch top and the arch shoulder are more significant) and the effective stress of the supporting structure exceed the strength design value. In addition, the maximum adequate pressure is distributed in the medial diaphragm wall. With the optimized blasting scheme, the range of the peripheral rock damage is reduced by a maximum of 67%, and the effective stress in the supporting structure is reduced by 25.9-64.8%. The research results are of great significance in terms of improving construction safety, economic efficiency, and project quality, as well as in promoting the research and development of new work methods for double-arch tunnels.

Ninety-day postoperative mortality and complications in continuous and unselected single-stage revisions for chronic periprosthetic joint infection.

PURPOSE: Single-stage revision has gained significant attention as a major surgical approach for periprosthetic joint infection (PJI). However, the 90-day mortality and complication profile of single-stage revision is poorly characterized. The purposes of this study were to determine the incidence rates of and identify the risk factors for 90-day postoperative mortality and complications of single-stage revision for chronic PJI. METHODS: A retrospective review was conducted on patients who underwent single-stage revision for PJI between August 2000 and May 2022. Patient demographics, 90-day mortality, and postoperative complications were recorded. Complications were categorized into systemic and local complications. Patients in this study were further categorized into knee and hip revision groups. Univariate and multivariate logistic regression analyses were performed to identify significant independent predictors of the outcome measures. RESULTS: 348 patients (144 knees and 204 hips) were included in this study. The 90-day mortality rate was 0.9%. The incidence rates of postoperative complications in knee and hip surgeries were 31.3% and 19.6%, respectively. The most common complication was deep-vein thrombosis (DVT). Rheumatoid arthritis (RA) was the independent predictor of mortality. In the knee revision group, fungal infection was identified as the independent predictor of recurrent PJI; regular alcohol use was predictive of wound dehiscence. Among hip PJI patients, age ≥ 80 years was independently associated with DVT; RA was found to be a predictor of dislocation and wound dehiscence. CONCLUSION: For continuous and unselected patients with chronic PJI, single-stage revision demonstrated a satisfactory 90-day mortality. Nevertheless, the 90-day postoperative complication rates after single-stage revision in both knee and hip groups were relatively high.

Biological Control of Rapeseed Clubroot (Plasmodiophora brassicae) using the Endophytic Fungus Didymella macrostoma P2.

Didymella macrostoma P2 was isolated from rapeseed (Brassica napus), and it is an endophyte of rapeseed and an antagonist of three rapeseed pathogens, Botrytis cinerea, Leptosphaeria biglobosa and Sclerotinia sclerotiorum. However, whether or not P2 has a suppressive effect on infection of rapeseed by the clubroot pathogen Plasmodiophora brassicae remains unknown. This study was conducted to detect production of antimicrobials by P2 and to determine efficacy of the antimicrobials and P2 pycnidiospores in suppression of rapeseed clubroot. Results showed that cultural filtrates (CF) of P2 in potato dextrose broth and the substances in pycnidiospore mucilages exuded from P2 pycnidia were inhibitory to P. brassicae. In the indoor experiment, seeds of the susceptible rapeseed cultivar Zhongshuang No.9 treated with P2 CF and the P2 spore suspension (P2 SS, 1 × 107 spores/ml) reduced clubroot severity by 31% to 70% on the 30-day-old seedlings compared to the control (seeds treated with water). P2 was re-isolated from the roots of the seedlings in the treatment of P2 SS, the average isolation frequency in the healthy roots (26%) was much higher than that (5%) in the diseased roots. In the field experiment, seeds of another susceptible rapeseed cultivar Huayouza 50 (HYZ50) treated with P2 CF, P2 CE (chloroform extract of P2 CF, 30 µg/ml) and P2 SS reduced clubroot severity by 29% to 48% on 60-day-old seedlings and by 28% to 59% on adult plants (220 days old) compared to the control treatment. The three P2 treatments on HYZ50 produced significantly (P < 0.05) higher seed yield than the control treatment on this rapeseed cultivar, and they even generated seed yield similar to that produced by the resistant rapeseed cultivar Shengguang 165R in one of the two seasons. These results suggest that D. macrostoma P2 is an effective biocontrol agent against rapeseed clubroot.

Impacts of ß-1, 3-N-acetylglucosaminyltransferases (B3GNTs) in human diseases.

Glycosylation modification of proteins is a common post-translational modification that exists in various organisms and has rich biological functions. It is usually catalyzed by multiple glycosyltransferases located in the Golgi apparatus. ß-1,3-N-acetylglucosaminyltransferases (B3GNTs) are members of the glycosyltransferases and have been found to be involved in the occurrence and development of a variety of diseases including autoimmunity diseases, cancers, neurodevelopment, musculoskeletal system, and metabolic diseases. The functions of B3GNTs represent the glycosylation of proteins is a crucial and frequently life-threatening step in progression of most diseases. In this review, we give an overview about the roles of B3GNTs in tumor, nervous system, musculoskeletal and metabolic diseases, describing the recent results about B3GNTs, in order to provide a research direction and exploration value for the prevention, diagnosis and treatment of these diseases.

Phthalate exposure aggravates periodontitis by activating NFκB pathway.

BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.

The value of MRI-based radiomics for evaluating early parotid gland injury in primary Sjögren's syndrome.

OBJECTIVE: This study aimed to evaluate the value of machine learning models (ML) based on MRI radiomics in diagnosing early parotid gland injury in primary Sjögren's syndrome (pSS). METHODS: A total of 164 patients (114 in the training cohort and 50 in the testing cohort) with pSS (n=82) or healthy controls (HC) (n=82) were enrolled. Itksnap software was used to perform two-dimensional segmentation of the bilateral parotid glands on T1-weighted (T1WI) and fat-suppressed T2-weighted imaging (fs-T2WI) images. A total of 1548 texture features of the parotid glands were extracted using radiomics software. A radiomics score (Radscore) was constructed and calculated. A t-test was used to compare the Radscore between the two groups. Finally, five machine learning models were trained and tested to identify early pSS parotid injury, and the performance of the machine learning models was evaluated by calculating the acceptance operating curve (ROC) and other parameters. RESULTS: The Radscores between the pSS and HC groups showed significant statistical differences (p<0.001). Among the five machine learning models, the Extra Trees Classifier (ETC) model performed high predictive efficacy in identifying early pSS parotid injury, with an AUC of 0.87 in the testing set. CONCLUSION: MRI radiomics-based machine learning models can effectively diagnose early parotid gland injury in primary Sjögren's syndrome.

Effects of Rainfall Exclusion Treatment on Photosynthetic Characteristics of Black Locust in the Sub-Humid Region of the Loess Plateau, China.

The mesic-origin species Robinia pseudoacacia L. (black locust) is widely planted in the semiarid and sub-humid areas of the Loess Plateau for the reforestation of vegetation-degraded land. Under the scenario of changing precipitation patterns, exploring the response of photosynthesis to drought allows us to assess the risk to sustainable development of these plantations. In this study, paired plots were established including the control and a treatment of 30% exclusion of throughfall (since 2018). The photosynthetic characteristics were investigated using a portable photosynthesis system for four periods in the full-leaf growing season of 2021-2022, the fourth and fifth years, on both treated and controlled sampling trees. Leaf gas exchange parameters derived from diurnal changing patterns, light response curves, and CO2 response curves showed significant differences except for period II (9-11 September 2021) between the two plots. The photosynthetic midday depression was observed in 2022 in the treated plot. Meanwhile, the decline of net photosynthetic rate in the treated plot was converted from stomatal limitation to non-stomatal limitation. Furthermore, we observed that black locust adapted to long-term water deficiency by reducing stomatal conductance, increasing water use efficiency and intrinsic water use efficiency. The results demonstrate that reduction in precipitation would cause photosynthesis decrease, weaken the response sensitivity to light and CO2, and potentially impair photosynthetic resilience of the plantations. They also provide insights into the changes in photosynthetic functions under global climate change and a reference for management of plantations.

In vitro immunoregulatory role of recombinant Ancylostoma ceylanicum calreticulin.

Ancylostoma ceylanicum is a zoonotic soil-derived nematode that parasitizes the intestines of humans and animals (dogs and cats), leading to malnutrition and iron-deficiency anemia. Helminth parasites secrete calreticulin (CRT), which regulates or blocks the host's immune response. However, no data on A. ceylanicum calreticulin (Ace-CRT) are available. We investigated the biological function of recombinant Ace-CRT (rAce-CRT). rAce-CRT showed reliable antigenicity and stimulated the proliferation of mouse splenocytes and canine peripheral blood mononuclear cells. Quantitative reverse-transcription PCR assays revealed that rAce-CRT primarily promoted the expression of T helper 2 cytokines, particularly IL-13, in canine peripheral blood lymphocytes. rAce-CRT inhibited complement-mediated sheep erythrocyte hemolysis in vitro. Our findings indicate that Ace-CRT plays an immunomodulatory role and may be a promising candidate molecule for a hookworm vaccine.

Bilateral chylothorax after left neck lymphadenectomy for thyroid cancer: A case report.

Introduction: Chylothorax is caused by lymphatic chyle fluid leaking back through the thoracic duct and accumulating in the pleural cavity. It is related to a thoracic duct injury or occlusion. It is rare to have bilateral chylothorax after cervical lymph node dissection for thyroid cancer diagnosis. Case report: A 28-year-old woman was admitted to our hospital with bilateral hypoechoic thyroid nodules and cervical lymph node abnormalities. She underwent thyroidectomy and lymphadenectomy but developed chylothorax 3 days after surgery. She was treated with bilateral thoracic drainage, electrolyte supplementation, and somatostatin, and was discharged 17 days post-treatment. Conclusion: Bilateral chylothorax is a rare complication of thyroid cancer surgery. Early diagnosis and treatment, especially the detection of dyspnea, are key. Also, unobstructed bilateral thoracic drainage, improved surgical skills, and reduced thoracic duct injuries can help reduce complications.

Involvement of GSTP1 in low dose radiation-induced apoptosis in GM12878 cells.

BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

miR615-3p inhibited FBLN1 and osteogenic differentiation of umbilical cord mesenchymal stem cells by associated with YTHDF2 in a m6 A-miRNA interaction manner.

To investigate the role and mechanism of FBLN1 in the osteogenic differentiation and bone regeneration by using umbilical cord mesenchymal stem cells (WJCMSCs). We found that FBLN1 promoted osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. It was showed that there was an m6 A methylation site in 3'UTR of FBLN1 mRNA, and the mutation of the m6 A site enhanced the stability of FBLN1 mRNA, subsequently fostering the FBLN1 enhanced osteogenic differentiation of WJCMSCs. YTHDF2 was identified as capable of recognizing and binding to the m6 A site, consequently inducing FBLN1 instability and repressed the osteogenic differentiation of WJCMSCs. Meanwhile, miR-615-3p negatively regulated FBLN1 by binding FBLN1 3'UTR and inhibited the osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. Then, we discovered miR-615-3p was found to regulate the functions of FBLN1 facilitated by YTHDF2 through an m6 A-miRNA regulation mechanism. We demonstrated that FBLN1 is critical for regulating the osteogenic differentiation potentials of WJCMSCs and have identified that miR615-3p mediated the decay of FBLN1 mRNA which facilitated by m6 A reading protein YTHDF2. This provided a novel m6 A-miRNA epigenetic regulatory pattern for MSC regulation and bone regeneration.

Fibroblast-like synoviocytes-derived exosomal circFTO deteriorates rheumatoid arthritis by enhancing N6-methyladenosine modification of SOX9 in chondrocytes.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes disability worldwide. Exosomes released by fibroblast-like synoviocytes in RA (RA-FLSs-Exos) play a role in the development of RA, and circular RNAs (circRNAs) are important for RA progression. This study aimed to investigate the molecular mechanisms underlying the effects of RA-FLSs-Exos in RA and identify the potential pathway responsible for these effects. METHODS: We initially conducted microarray analysis to identify dysregulated circRNAs in exosomes associated with RA. We then co-cultured isolated RA-FLSs-Exos with chondrocytes to examine their role in RA. In vivo experiments were performed using collagen-induced arthritis mouse models, and circFTO knockdown was achieved through intra-articular injection of AAV5 vectors. RESULTS: Our findings revealed increased expression of circFTO in both RA-FLSs-Exos and synovial tissues from patients with RA. Exosomal circFTO hindered chondrocyte proliferation, migration, and anabolism while promoting apoptosis and catabolism. Mechanistically, we discovered that circFTO facilitates the formation of methyltransferases complex to suppress SRY-related high-mobility group box 9 (SOX9) expression with assistance from YTH domain family 2 (YTHDF2) through an m6A-dependent mechanism. Furthermore, inhibition of circFTO improved symptoms of RA in vivo. CONCLUSION: Taken together, our study demonstrates that exosomal circFTO derived from FLSs contributes to the progression of RA by targeting SOX9. These findings highlight a promising target for treating RA.

Group 1 innate lymphoid cell activation via recognition of NKG2D and liver resident macrophage MULT-1: Collaborated roles in triptolide induced hepatic immunotoxicity in mice.

Triptolide (TP) is the major bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., a traditional Chinese medicinal plant categorized within the Tripterygium genus of the Celastraceae family. It is recognized for its therapeutic potential in addressing a multitude of diseases. Nonetheless, TP is known to exhibit multi-organ toxicity, notably hepatotoxicity, which poses a significant concern for the well-being of patients undergoing treatment. The precise mechanisms responsible for TP-induced hepatotoxicity remain unresolved. In our previous investigation, it was determined that TP induces heightened hepatic responsiveness to exogenous lipopolysaccharide (LPS). Additionally, natural killer (NK) cells were identified as a crucial effector responsible for mediating hepatocellular damage in this context. However, associated activating receptors and the underlying mechanisms governing NK cell represented innate lymphoid cell (ILC) activation remained subjects of inquiry and were not yet investigated. Herein, activating receptor Killer cell lectin like receptor K1 (NKG2D) of group 1 ILCs was specifically upregulated in TP- and LPS-induced acute liver failure (ALF), and in vivo blockade of NKG2D significantly reduced group 1 ILC mediated cytotoxicity and mitigated TP- and LPS-induced ALF. NKG2D ligand UL16-binding protein-like transcript 1 (MULT-1) was found upregulated in liver resident macrophages (LRMs) after TP administration, and LRMs did exhibit NK cell activating effect. Furthermore, M1 polarization of LRMs cells was observed, along with an elevation in intracellular tumor necrosis factor (TNF)-α levels. In vivo neutralization of TNF-α significantly alleviated TP- and LPS-induced ALF. In conclusion, the collaborative role of group 1 ILCs and LRMs in mediating hepatotoxicity was confirmed in TP- and LPS-induced ALF. TP-induced MULT-1 expression in LRMs was the crucial mechanism in the activation of group 1 ILCs via MULT-1-NKG2D signal upon LPS stimulation, emphasizing the importance of infection control after TP administration.

Fine mapping of ClLOX, a QTL for powdery mildew resistance in watermelon (Citrullus lanatus L.).

KEY MESSAGE: ClLOX, is located on chromosome 2 and encodes a lipoxygenase gene, which induced watermelon powdery mildew resistance by inhibiting pathogen spread. Powdery mildew is one of the most severe fungal diseases reducing yield and quality of watermelon (Citrullus lanatus L.) and other cucurbit crops. Genes responsible for powdery mildew resistance in watermelon are highly valuable. In this study, we first identified the QTL pm-lox for powdery mildew resistance in watermelon, located within a 0.93 Mb interval of chromosome 2, via XP-GWAS method using two F2 populations. The F2:3 families from one of the F2 populations were then used for fine-mapping the pm-lox locus into a 9,883 bp physical region between 29,581,906 and 29,591,789, containing only two annotated genes. Of these, only ClG42_02g0161300 showed a significant differential expression between the resistant and susceptible lines after powdery mildew inoculation based on RNA sequencing (RNA-seq) and qRT-PCR analysis, and is designated ClLOX. Derived Cleaved Amplified Polymorphic Sequence (dCAPs) markers were developed and validated. In addition, our tests showed that the resistance was anti-spread rather than anti-infection of the pathogen. This study identified a new resistance gene (ClLOX), provided insights into the mechanism of powdery mildew resistance, and developed a molecular marker for watermelon breeding.

Structure Guided Discovery of Novel Pan Metallo-ß-Lactamase Inhibitors with Improved Gram-Negative Bacterial Cell Penetration.

The use of ß-lactam (BL) and ß-lactamase inhibitor combination to overcome BL antibiotic resistance has been validated through clinically approved drug products. However, unmet medical needs still exist for the treatment of infections caused by Gram-negative (GN) bacteria expressing metallo-ß-lactamases. Previously, we reported our effort to discover pan inhibitors of three main families in this class: IMP, VIM, and NDM. Herein, we describe our work to improve the GN coverage spectrum in combination with imipenem and relebactam. This was achieved through structure- and property-based optimization to tackle the GN cell penetration and efflux challenges. A significant discovery was made that inhibition of both VIM alleles, VIM-1 and VIM-2, is essential for broad GN coverage, especially against VIM-producing P. aeruginosa. In addition, pharmacokinetics and nonclinical safety profiles were investigated for select compounds. Key findings from this drug discovery campaign laid the foundation for further lead optimization toward identification of preclinical candidates.

Research insights into the chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM): their roles in various tumors.

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.

A second species of Megipocerus Zakhvatkin (Hemiptera: Cicadellidae: Eurymelinae).

A second species of Megipocerus, M. hunanensis Zhang sp. nov., is recognized here from China, which can be easily distinguished from the type species, M. mordvilkoi Zakhvatkin, by numerous dark brown to black markings on the head and thorax, shorter male pygofer bearing four mastoid processes with longer process and short subapical processes. And the female of M. mordvilkoi was recorded in China for the first time, and an illustrated key is also provided.