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Abstract B7-H3 (CD276), a member of the B7 family of proteins, is a key player in cancer progression. This immune checkpoint molecule is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. In addition to its immune checkpoint function, B7-H3 has been linked to tumor cell proliferation, metastasis, and therapeutic resistance. Furthermore, its drastic difference in protein expression levels between normal and tumor tissues suggests that targeting B7-H3 with drugs would lead to cancer-specific toxicity, minimizing harm to healthy cells. These properties make B7-H3 a promising target for cancer therapy. Recently, important advances in B7-H3 research and drug development have been reported, and these new findings, including its involvement in cellular metabolic reprograming, cancer stem cell enrichment, senescence and obesity, have expanded our knowledge and understanding of this molecule, which is important in guiding future strategies for targeting B7-H3. In this review, we briefly discuss the biology and function of B7-H3 in cancer development. We emphasize more on the latest findings and their underlying mechanisms to reflect the new advances in B7-H3 research. In addition, we discuss the new improvements of B-H3 inhibitors in cancer drug development.

Abstract BRD7 functions as a crucial tumor suppressor in numerous malignancies including nasopharyngeal carcinoma (NPC). However, its function and exact mechanisms involved in tumor progression are not well understood. Here, we found that the B7BS was a potential enhancer region of BIRC2, and BRD7 negatively regulated the transcriptional activity and expression of BIRC2 by targeting the activation of the BIRC2 enhancer. Moreover, BIRC2 promoted cell proliferation, migration, invasion as well as xenograft tumor growth and metastasis in vivo, thus functioning as an oncogene in NPC. Furthermore, the recovery of BIRC2 expression could rescue the inhibitory effect of BRD7 on cell proliferation, migration, invasion and xenograft tumor growth and metastasis. In addition, BIRC2 was highly-expressed in NPC tissues, and positively correlated with the TNM stage and negatively correlated with the expression of BRD7. Therefore, these results suggest that BRD7 suppresses tumor growth and metastasis thus functioning as a tumor suppressor at least partially by negatively regulating the enhancer activity and expression of BIRC2, and targeting the BRD7/BIRC2 regulation axis might be a potential strategy for the diagnosis and treatment of NPC.

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.

Aiming at the problems that it is difficult to control the expansion force of lime-sand pile in the foundation correcting and how the upper existing structural pressure affects the expansion force of lime-sand pile, this paper adopts a new type of lime-sand pile reaction tester to carry out the experimental research on the expansion force of lime-sand pile under the influences of different pre-pressure, different mixing ratios, different heights, and different granular sizes. The purpose of this paper is to explore the influence of the pre-pressure brought by the existing building structure on the expansion force of the lime-sand pile and the coupling effect of the pre-pressure and other influencing factors on the expansion force of the lime-sand pile through the multi-parameter test. The results show that with the increase in pre-pressure, the expansion force of the lime-sand pile shows the trend of increasing first and then decreasing when the pre-pressure is 0.88 KN, the effect is most obvious and its expansion force can be increased by 14.9%. Within a certain range, the larger the proportion of quicklime is, the lower the expansion reaction force is. The expansion force of the lime-sand pile with the ratio of lime/sand/soil of 5:4:1 is the most ideal, and its value reaches 10.2 KN, which is 10% and 15.3% higher than the rest of the two groups, respectively. Within a certain range, the effect of specimen height change on the expansion force of the lime-sand pile is almost negligible. The smaller particle size of quicklime makes its reaction speed faster, the reaction degree is more full, and the expansion force is greater. The expansion force of the small particle size group was 12.1% and 34.2% higher than that of the medium and large particle size groups, respectively.

Background Internet gaming disorder (IGD) is an ideal model to study the mechanisms underlying synaptic deficits in addiction as it eliminates the confounding effects of substance use. Synaptic loss and deficits are hypothesised to underlie the enduring maladaptive behaviours and impaired cognitive function that contribute to IGD.Aims This study aimed to determine whether subjects with IGD have lower synaptic density than control subjects and the relationship between synaptic density and IGD severity.Methods Eighteen unmedicated subjects diagnosed with current IGD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and 16 demographically matched healthy controls (HCs) participated in the study and underwent 18F-labelled difluoro-analogue of UCB-J (18F-SynVesT-1) positron emission tomography scans to assess the density of synaptic vesicle glycoprotein 2A (SV2A). The Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), Barratt Impulsiveness Scale Version 11 (BIS-11), Stroop Colour-Word Test (SCWT), stop-signal paradigms and N-back tasks were administered to all subjects.Results Patients with IGD had significantly higher scores on the IGDS9-SF, HAMD, HAMA and BIS-11 than HCs. HCs performed better on the two-back and SCWT tests as well as in terms of stop-signal reaction times (SSRTs) in the stop-signal paradigms than patients with IGD. Lower uptake was found in the bilateral putamen, right pregenual anterior cingulate cortex and Rolandic operculum of patients with IGD compared with HCs. Furthermore, in the IGD group, IGDS9-SF scores and daily gaming hours were negatively correlated with the standardised uptake value ratios of 18F-SynVesT-1 in the bilateral putamen. Longer SSRTs were significantly associated with lower SV2A density in the right pregenual anterior cingulate cortex and right Rolandic operculum.Conclusions The in vivo results in this study suggest that lower synaptic density contributes to the severity and impairments in inhibitory control of IGD. These findings may provide further incentive to evaluate interventions that restore synaptic transmission and plasticity to treat IGD.

Traditional underwater detectors struggle to match the demands of visual observation and icon detection because of the underwater optical pictures' color distortion, uneven illumination, and excessive noise levels. In this paper, a lightweight deep-water object detection network is proposed, which consists of three key components, namely image restoration, color transformation, and object detection. First, we propose a lightweight attention module for the problems of color distortion and uneven illumination in underwater images. This module pays more attention to the areas with a greater influence of underwater color when dealing with different types of poor-quality images. Second, to reduce the computational complexity of object detection, we propose a color conversion module based on the laplacian pyramid decomposition. This module incorporates multi-scale features to effectively address the loss of details in the brightest or darkest regions. Finally, we propose a multi-scale dense residual object detection network. The network applies a multi-scale kernel to an improved residual module to realize the extraction and fusion of feature information of multiple receptive fields. Furthermore, to deal with the problem of underwater small-sample object detection, we propose a mutually exclusive loss function. The mutual exclusion loss promotes the update of network parameters so that the classes with different characteristics of samples generated by the network are mutually exclusive. We ran tests on the Pycharm platform to show that the suggested lightweight joint underwater object identification algorithm outperformed the most sophisticated ones. The proposed system was put to the test in an intricate underwater setting, achieving 92.56 percent accuracy and 19.2 frames per second.

ABSTRACT The host innate immune system’s defense against viral infections depends heavily on type I interferon (IFN-I) production. Research into the mechanisms of virus-host interactions is essential for developing novel antiviral therapies. In this study, we compared the effect of the five members of the microRNA-200 (miR-200) family on IFN-I production during viral infection and found that miR-200b-3p displayed the most pronounced regulatory effect. During viral infection, we discovered that the transcriptional level of microRNA-200b-3p (miR-200b-3p) increased with the infection of influenza virus (IAV) and vesicular stomatitis virus (VSV), and miR-200b-3p production was modulated by the activation of the ERK and p38 pathways. We identified cAMP response element binding protein (CREB) as a novel transcription factor that binds to the miR-200b-3p promoter. MiR-200b-3p reduces NF-κB and IRF3-mediated IFN-I production by targeting the 3′ untranslated region (3′ UTR) of TBK1 mRNA. Applying miR-200b-3p inhibitor enhances IFN-I production in IAV and VSV-infected mouse models, thus inhibiting viral replication and improving mouse survival ratio. Importantly, in addition to IAV and VSV, miR-200b-3p inhibitors exhibited potent antiviral effects against multiple pathogenic viruses threatening human health worldwide. Overall, our study suggests that miR-200b-3p might be a potential therapeutic target for broad-spectrum antiviral therapy. IMPORTANCE The innate immune response mediated by type I interferon (IFN-I) is essential for controlling viral replication. MicroRNAs (miRNAs) have been found to regulate the IFN signaling pathway. In this study, we describe a novel function of miRNA-200b-3p in negatively regulating IFN-I production during viral infection. miRNA-200b-3p was upregulated by the MAPK pathway activated by IAV and VSV infection. The binding of miRNA-200b-3p to the 3′ UTR of TBK1 mRNA reduced IFN-I activation mediated by IRF3 and NF-κB. Application of miR-200b-3p inhibitors exhibited potent antiviral effects against multiple RNA and DNA viruses. These results provide fresh insight into understanding the impact of miRNAs on host-virus interactions and reveal a potential therapeutic target for common antiviral intervention.

ObjectiveTo evaluate the clinical efficacy and safety of a short course of blinatumomab in children with refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R-BCP-ALL).MethodsThe clinical data of 33 R/R BCP-ALL children aged 0–18 years who underwent a short course of blinatumomab (14 days) between August 2021 and November 2022 were retrospectively collected and analyzed.ResultsAmong 33 patients with BCP-ALL, 26 achieved complete remission (CR), with a total remission rate of 78.8% (26/33). The duration of remission was approximately 14 days. Of the 7 children without CR, 5 were still in remission at 28 days. In 11 patients with refractory disease and 22 with recurrence, the remission rates were 90.9% (10/11) and 72.7% (16/22), respectively. The overall survival (OS) rates of the 26 patients with CR and seven patients without CR were 96.1% and 57.1% (p = 0.002), respectively, and the disease-free survival (DFS) rates were 96.1% and 42.9% (p

Summary: Background: Inhibiting vascular endothelial growth factor (VEGF) function can improve the efficacy of immunotherapy by modulating the tumor immune microenvironment. AK112 is the first-in-class humanized IgG1 bispecific antibody targeting programmed death-1 (PD-1) and VEGF. This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: This open-label, multicenter, phase II clinical trial was conducted in 11 hospitals in China. Eligible participants were adults aged 18–75 years with locally advanced or metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, and an estimated life expectancy of at least 3 months. The participants were categorized into three cohorts based on prior therapy and functional genomic alterations. Patients in cohort 1 were previously untreated advanced NSCLC, had no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene modifications, and received AK112 combined with pemetrexed (500 mg/m2) for non-squamous (non-sq)-NSCLC or paclitaxel (175 mg/m2) for sq-NSCLC plus carboplatin (area under the curve of 5 mg/mL per min) for four cycles, followed by AK112 with pemetrexed for non-sq-NSCLC and AK112 alone for sq-NSCLC as maintenance therapy. The participants in cohort 2 had advanced NSCLC with EGFR-sensitive mutations, failed previous EGFR-tyrosine kinase inhibitor (TKI) therapy, and received pemetrexed plus AK112 and carboplatin for four cycles, followed by pemetrexed plus AK112 as maintenance therapy. The participants in cohort 3 had advanced NSCLC who failed systemic platinum-based chemotherapy and anti-PD-1/programmed death-ligand 1 (PD-L1) treatments and received AK112 plus docetaxel (75 mg/m2). Two dosages of AK112 (10 or 20 mg/kg) were examined in each cohort, and the drug was administered intravenously on day 1 of each 3-week treatment cycle. The primary endpoints were the investigator-assessed objective response rate (ORR) and safety. This study was registered with ClinicalTrials.gov (NCT04736823). Findings: Eighty-three patients were enrolled from February 2021 to August 2022 and received the study treatment. Cohorts 1, 2, and 3 had 44, 19, and 20 patients, respectively. The confirmed ORR was 53.5% (23/43) [95% CI, 36.9–67.1], 68.4% (13/19) [95% CI, 43.4–87.4], and 40.0% (8/20) [95% CI, 19.1–63.9] in cohorts 1, 2, and 3, respectively. In cohort 1, the median PFS was not reached, and the 12-month PFS rate was 59.1%. In cohorts 2 and 3, the median PFS were 8.5 [95% CI, 5.5-NE] and 7.5 [95% CI, 2.3-NE] months, and the 12-month PFS rates were 35.5% and 44.5%, respectively. The most common grade ≥3 treatment-related adverse events were decreased white blood cell count [7 (8.4%)], neutropenia [5 (6.0%)], thrombocytopenia [2 (2.4%)], anemia [4 (4.8%)], and myelosuppression [2 (2.4%)]. Interpretation: AK112 plus platinum-doublet showed promising antitumor activity and safety not only in first-line treatment of advanced NSCLC patients without driver mutation but also in patients with EGFR-functional mutation who failed previous EGFR-TKI therapy and advanced NSCLC patients who failed prior systemic platinum-based chemotherapy and PD-1/PD-L1 inhibitor treatments, suggesting a valuable potential new treatment option for this patient population. Funding: Akeso Biopharma, Inc., Zhongshan, China, and National Natural Science Foundation of China.

Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite, 24-hydroxycholesterol (24HC), also shows competence in inhibiting the replication of multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 24HC can increase the cholesterol concentration in multivesicular body (MVB)/late endosome (LE) by disrupting the interaction between OSBP and VAPA, resulting in viral particles being trapped in MVB/LE, ultimately compromising VSV and RABV entry into host cells. These findings provide the first evidence that brain cholesterol oxidation products may play a critical role in viral infection.

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism, a randomized controlled trial was conducted involving boys who were 6–12 months old at surgery and were diagnosed with clinically palpable, inguinal undescended testis. Between June 2021 and December 2021, these boys at Fujian Maternity and Child Health Hospital (Fuzhou, China) and Fujian Children's Hospital (Fuzhou, China) were enrolled. Block randomization with a 1:1 allocation ratio was employed. The primary outcome was testicular function assessed by testicular volume, serum testosterone, anti-Müllerian hormone (AMH), and inhibin B (InhB) levels. Secondary outcomes included operative time, amount of intraoperative bleeding, and postoperative complications. Among 577 screened patients, 100 (17.3%) were considered eligible and enrolled in the study. Of the 100 children who completed the 1-year follow-up, 50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy. The testicular volume, serum testosterone, AMH, and InhB levels in both groups increased markedly after surgery (all P < 0.05), but there were no apparent differences between groups at 6 months and 12 months after operation (all P > 0.05). No differences between the scrotal and inguinal groups were noted regarding the operative time (P = 0.987) and amount of intraoperative bleeding (P = 0.746). The overall complication rate (2.0%) of the scrotal group was slightly lower than that of the inguinal group (8.0%), although this difference was not statistically significant (P > 0.05). Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism, with similar operative status and postoperative complications. Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.

Harnessing exotic optical forces promises a plethora of biophysical applications and novel light-matter interactions. The exotic optical pulling force (OPF) and optical lateral force (OLF) have been studied separately, yet synthesizing both candidates simultaneously remains an unsolved challenge and could offer a more powerful manoeuvre of particles. Here, we report a coordinated scheme to harness these two forces together and present a dynamically controlled two-dimensional (2D) microvehicle. The strategy is to leverage unexplored helicity-dependent features of both forces, while the particle size and incident angle of light can also reverse optical forces. The underlying physics of the pulling-lateral force is beyond the dipole approximation, and can be the combined effect from the linear momentum transfer, spin-orbit interactions, etc. Notably, the ratio of both forces can be dynamically and arbitrarily controlled by the ellipticity of incident light solely. The configured 2D microvehicle provides a nontrivial recipe other than using metastructures which require exquisite designs and subtle fabrication processes.

For many years, surgical treatment of buried penis in children has been researched by several scholars, and numerous methods exist. This study aimed to explore the clinical effect of a modified fixation technique in treating buried penis in children. Clinical data of 94 patients with buried penis who were treated using the modified penile fixation technique from March 2017 to February 2019 in Fujian Maternity and Child Health Hospital (Fuzhou, China) were retrospectively collected, compared, and analyzed. Clinical data of 107 patients with buried penis who were treated using traditional penile fixation technique from February 2014 to February 2017 were chosen for comparison. The results showed that at 6 months and 12 months after surgery, the penile lengths in the modified penile fixation group were longer than those in the traditional penile fixation group (both P < 0.05). The incidence of postoperative skin contracture and penile retraction in the modified penile fixation group was less than that in the traditional penile fixation group (P = 0.034 and P = 0.012, respectively). When the two groups were compared in terms of parents' satisfaction scores, the scores for penile size, penile morphology, and voiding status in the modified penile fixation group were higher than those in the traditional penile fixation group at 2-week, 6-month, and 12-month follow-ups after surgery (all P < 0.05). We concluded that the modified penile fixation technique could effectively reduce the incidence of skin contracture and penile retraction and improve the penile length and satisfaction of patients' parents.

With an increase in the electrification of end-use sectors, various resources on the demand side provide great flexibility potential for system operation, which also leads to problems such as the strong randomness of power consumption behavior, the low utilization rate of flexible resources, and difficulties in cost recovery. With the core idea of “access over ownership”, the concept of the sharing economy has gained substantial popularity in the local energy market in recent years. Thus, we provide an overview of the potential market design for the sharing economy in local energy markets (LEMs) and conduct a detailed review of research related to local energy sharing, enabling technologies, and potential practices. This paper can provide a useful reference and insights for the activation of demand-side flexibility potential. Hopefully, this paper can also provide novel insights into the development and further integration of the sharing economy in LEMs.

BRD4-NUT’s bipartite binding and activation of p300 in NUT carcinoma nucleates a feed-forward spread of histone hyperacetylation and chromatin condensation that sustains aberrant pro-proliferation gene transcription and perpetual tumor cell growth.

Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the anti-IgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in anti-IgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.

Background: Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases. We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the prevention of subclinical thyroid dysfunction (SCTD). Therefore, we designed a large-scale cohort study to examine whether mushrooms consumption is a protective factor for SCTD in adults. Methods: This prospective cohort study investigated 6631 participants (mean age: (45.0 ± 10.2) years; 55.1 % men). Edible mushrooms consumption was measured at baseline using a validated food frequency questionnaire. SCTD was defined as abnormal serum thyroid-stimulating hormone levels and normal free thyroxine. Cox proportional hazards regression models were used to examine the association of edible mushrooms consumption with incident SCTD. Results: During follow-up period, a total of 262 new cases of SCTD were identified, the incidence rate of subclinical hypothyroidism was 8.9/1000 person-years and subclinical hyperthyroidism was 7.2/1000 person-years. After adjusting potential confounding factors, the multivariable hazard ratios (95 % confidence intervals) for subclinical hypothyroidism were 1.00 (reference) for almost never, 0.53 (0.29, 0.97) for 1–3 times/week and 0.30 (0.10, 0.87) for ≥ 4 times/week (P for trend = 0.02). It also showed edible mushrooms consumption was inversely associated with subclinical hypothyroidism in obese individuals but not non-obese individuals, the final hazard ratios (95 % confidence intervals) were 0.14 (0.03, 0.73) (P for trend < 0.01). Conclusions: his population-based prospective cohort study has firstly demonstrated that higher edible mushrooms consumption was significantly associated with lower incidence of subclinical hypothyroidism among general adult population, especially in obese individuals.

Air traffic complexity indicators play an essential role in measuring operational performance and controller workload. However, current studies mainly depend on the manual scoring method to scale performance or workload. This paper focuses on arrival operations and presents a data-driven strategy to establish the correlation between complexity and performance to avoid the subjectivity of the currently used manual scoring method. Firstly, we present twenty-six indicators for describing air traffic complexity and two indicators for arrival operational performance. Secondly, the clustering method distinguishes peak and off-peak situations for arrival operation. Moreover, clustering results are compared to investigate the correlation between complexity and performance initially. Thirdly, the classification method is adopted to determine such correlation further. In addition, we also identify the affecting factors which could influence operational performance. Finally, trajectories of arrival aircraft landing at Guangzhou Baiyun International Airport (ZGGG) are used for case validation. The results indicate that there is a strong correlation between complexity and performance. The accuracy and precision of classification are approximately 90%. Furthermore, the number of aircraft significantly impacts the arrival operational performance within TMA.

Highlights The whole bamboo mere made directly into cellulose composites, which greatly reduced massive energy consumption from the mechanical pre-processing process. The wall thickness of transparent whole bamboo can reach 6.23 mm. The modified whole bamboo possesses excellent optical transmittance of about 60% at 6.23 mm, the illuminance of 1000 luminance (lux), water absorption stability (the mass change rate less than 4%), longitudinal tensile strength (46.40 MPa), and surface properties (80.2 HD). The combination of excellent transmittance, mechanical properties, surface properties, thermal performance, and electromagnetic shielding properties makes this composite attractive in areas such as transparent, energy-saving, and electromagnetic shielding buildings.

The leaf is the main photosynthetic organ of plants, and it plays a significant role in the yield of crop species. Identifying the causal mutations and candidate genes that underlie leaf phenotypic variation is an important breeding target in soybean grain yield improvement. An ethyl methyl sulfonate (EMS)-induced soybean mutant DWARFCRINKLEDLEAF1 (DCL1) with an aberrant crinkled leaf phenotype was identified in the background of the soybean cultivar Zhongpin 661 (Zp661). We constructed an F2 segregating population from a cross between Zp661 and DCL1 in order to investigate the genomic locus associated with the crinkled leaf trait. Using bulk segregant analysis (BSA) combined with the whole-genome resequencing method, the Euclidean distance (ED) correlation algorithm detected 12 candidate genomic regions with a total length of 20.32 Mb that were linked to the target trait. Following a comparative analysis of the sequence data for the wild-type and mutant pools, only one single nucleotide mutation (C:G>T:A) located on the first exon of Glyma.19G207100 was found to be associated with the trait. Candidate gene validation based on a CAPS marker derived from the detected single-nucleotide polymorphism (SNP) indicated a nucleotide polymorphism between the two parents. Therefore, our findings reveal that Glyma.19G207100, which is renamed as GLYCINE MAX DWARF CRINKLED LEAF 1 (GmDCL1), is a promising candidate gene involved in the morphogenesis of the crinkled leaf trait of the soybean mutant DCL1. This study provides a basis for the functional validation of this gene, with prospects for soybean breeding targeting grain yield enhancement.

Background Acute kidney injury (AKI) is not a rare complication during anti-tuberculosis treatment in some patients with pulmonary tuberculosis (PTB). We aimed to develop a risk prediction model for early recognition of patients with PTB at high risk for AKI during anti-TB treatment.Methods This retrospective cohort study assessed the clinical baseline, and laboratory test data of 315 inpatients with active PTB who were screened for predictive factors from January 2019 to June 2020. The elements were analyzed by logistic regression analysis. A nomogram was established by the results of the logistic regression analysis. The prediction model discrimination and calibration were evaluated by the concordance index (C-index), ROC curve, and Hosmer-Lemeshow analysis.Results A total of 315 patients with PTB were enrolled (67 patients with AKI and 248 patients without AKI). Seven factors, including microalbuminuria, hematuria, cystatin-C (CYS-C), albumin (ALB), creatinine-based estimated glomerular filtration rates (eGFRs), body mass index (BMI), and CA-125 were acquired to develop the predictive model. According to the logistic regression, microalbuminuria (OR = 3.038, 95%CI 1.168–7.904), hematuria (OR = 3.656, 95%CI 1.325–10.083), CYS-C (OR = 4.416, 95%CI 2.296–8.491), and CA-125 (OR = 3.93, 95%CI 1.436–10.756) were risk parameter, while ALB (OR = 0.741, 95%CI 0.650–0.844) was protective parameter. The nomogram demonstrated good prediction in estimating AKI (C-index= 0.967, AUC = 0.967, 95%CI (0.941–0.984), sensitivity = 91.04%, specificity = 93.95%, Hosmer-Lemeshow analysis SD = 0.00054, and quantile of absolute error = 0.049).Conclusions Microalbuminuria, hematuria, ALB reduction, elevated CYS-C, and CA-125 are predictive factors for the development of AKI in patients with PTB during anti-TB treatments. The predictive nomogram based on five predictive factors is achieved good risk prediction for AKI during anti-TB treatments.

Abstract Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.

AIM: To evaluate the outcome of endoscopic dacryocystorhinostomy (En-DCR) with mucosal anastomosis in chronic dacryocystitis patients, with various categories of ethmoid sinuses. METHODS: Between July 2015 and September 2019, 1439 adult patients, representing 1623 affected eyes, presented with chronic dacryocystitis and were scheduled for En-DCR. The categories of ethmoid sinuses were preoperatively determined, using computed tomography-dacryocystography (CT-DCG), and were classified as category 1 (C1), category 2 (C2), and category 3 (C3). No sinuses anterior to the posterior lacrimal crest defined as C1. Sinuses found between the anterior edge of the lacrimal bone and the posterior lacrimal crest defined as C2. Sinuses found anterior to the lacrimal bone suture defined as C3. At the end of surgery, the dacryocyst and nasal mucosa were anastomosed in C1, and the dacryocyst mucosa and anterior ethmoid sinus were anastomosed in C2 and C3 ethmoid sinus patients. The surgical success rate and related complications, in patients with 3 categories of ethmoid cells, were monitored and documented. RESULTS: Postoperative data was obtained for 179 C1 affected eyes, 878 C2 affected eyes, and 432 C3 affected eyes. The overall success rate of En-DCR was 93.0% (1385/1489). Additionally, the success rates were comparable among the different ethmoid categories at 12mo post operation. We demonstrated that the major reason for surgical failure was intranasal ostial closure, due to granulation or scar tissue. CONCLUSION: En-DCR is a feasible and highly effective primary treatment for chronic dacryocystitis. To ensure surgical success, the surgery protocol must be designed in accordance with the category of ethmoid sinuses present in individual patient.