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Glioma is the most common primary intracranial tumors. Although great achievements have been made in the treatment, the efficacy is still unsatisfactory, which imposes a hefty burden on patients and society. Therefore, the exploration of new and effective anti-glioma drugs is urgent. Human glioma cell lines U251 and LN229 were included in the study. Cell proliferation was detected by cell counting kit-8 (CCK8), plate clone formation assay, EdU incorporation assay and xCELLigence real-time cell analyzer. Cell apoptosis was evaluated by TUNEL assay and flow cytometry. Then, transwell assay was used for assessing the migration. Moreover, tumor xenograft model was established to examine the effect of scutellarin (SCU) and lidocaine on the growth of glioma in vivo. Lastly, western blot was performed to detect the protein level of epidermal growth factor receptor (EGFR). In present study, we found that SCU and lidocaine suppressed the proliferation and migration, and induced the apoptosis of human glioma cell lines, including U251 and LN229 cells, in a dose-dependent manner in vitro. Moreover, the combination of SCU and lidocaine further restrained the proliferation and migration ability of U251 and LN229 cells, while induced their apoptosis in vitro. Additionally, SCU and lidocaine also inhibited the growth of glioma in vivo, and the effect of the combination was better. Above all, the toxicity of SCU and its combination with lidocaine was low to normal astrocytes and neurons. Mechanistically, the effect of SCU and its combination with lidocaine on glioma cells was partially associated with the repression of EGFR signaling. Scutellarin and lidocaine exerted a synergistic effect on suppressing the proliferation and migration and inducing the apoptosis of glioma cells, which was partly associated with the repression of EGFR signaling.

A enantioselective tandem transformation, concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs), in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, providing highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one made from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione in iridium-catalyzed allylic enolization involving keto-enol isomerization is accomplished under mild conditions. The chemoselectivity, regioselectivity, and enantioselectivity are facilitated by the quaternary carbon and adjusting the reaction conditions. This method provides the substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with high level of chemo-, regio-, and enantioselectivities. The chiral carbon-fluorine bond formation is induced by an adjacent chiral carbon center of the allylated 3-hydroxy-6,6-dimethylcyclohex-2-en-1-one, as well.

This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome (KS) who underwent preimplantation genetic testing (PGT) with frozen-thawed testicular spermatozoa. Microdissection testicular sperm extraction (micro-TESE) was performed for sperm retrieval. Next-generation sequencing (NGS) was conducted for embryo analysis. A total of 18 couples aged ≤35 years were included, and 22 oocyte retrieval cycles were completed. Euploidy was detected in 29 of 45 (64.4%) embryos. Additionally, the numbers of aneuploid and mosaic embryos detected were 8 (17.8%) and 8 (17.8%), respectively, regardless of a lack of sex chromosome abnormalities. Finally, 13 couples with euploid embryos completed 14 frozen embryo transfer (FET) cycles. Ten couples had clinical pregnancies, and 6 of them had already delivered 5 healthy babies and 1 monozygotic twin. There were also 4 ongoing pregnancies and 2 biochemical pregnancies, but no early pregnancy loss was reported. Based on our results, we speculate that for KS patients, when sperm can be obtained by micro-TESE, the cryopreservation strategy makes the ovarian stimulation procedure more favorable for female partners. The paternal genetic risk of sex chromosome abnormalities in their offspring is extremely low in men with KS. In addition to PGT, the intracytoplasmic sperm injection (ICSI) procedure is comparably effective but more economical for young nonmosaic KS couples. ICSI should be offered as an option for such couples, but monitoring by prenatal genetic diagnosis is recommended.

Background Lower respiratory infections (LRIs) remain a leading cause of death and disability. AMR is considered as a paramount twenty-first century public health threat. Objectives To assess the global burden of AMR-associated LRIs using data from Global Burden of Disease (GBD) 2021. Methods Mortality data, including absolute counts, age-standardized mortality rates (ASMRs), and AMR-specific metrics, were extracted from the GBD 2021 dataset and stratified by demographic characteristics (age groups, sex), geographic regions, and socioeconomic status (SDI tiers). Results From 1990 to 2021, both absolute death counts and ASMRs demonstrated significant declines (EAPC: − 2.09); mortality burden (the death counts and ASMRs) caused by bacteria with AMR are 2 to 3 times that of bacteria with AMS; highest burden was observed in low-SDI regions and increasing trends were noted among older adults (≥ 50 years); S. pneumoniae dominated overall mortality, and S. aureus showed concerning upward trends; the mortality related to carbapenem-resistant A. Baumannii, E. coli, K. pneumoniae, and P. aeruginosa was on the rise. Conclusions While overall burden of AMR-associated LRIs mortality shows a declining trajectory, significant disparities persist across SDI strata. The emergence of resistance to last-resort antimicrobials of the leading bacterial pathogens highlights the urgent need for the prevention and control of AMR.

BackgroundThe rising prevalence of cystic renal lesions (CRLs) detected by computed tomography necessitates better identification of the malignant cystic renal neoplasms since a significant majority of CRLs are benign renal cysts. Using arterial phase CT scans combined with pathology diagnosis results, a fusion feature-based blending ensemble machine learning model was created to identify malignant renal neoplasms from cystic renal lesions (CRLs). Histopathology results were adopted as diagnosis standard. Pretrained 3D-ResNet50 network was selected for non-handcrafted features extraction and pyradiomics toolbox was selected for handcrafted features extraction. Tenfold cross validated least absolute shrinkage and selection operator regression methods were selected to identify the most discriminative candidate features in the development cohort. Feature’s reproducibility was evaluated by intra-class correlation coefficients and inter-class correlation coefficients. Pearson correlation coefficients for normal distribution and Spearman's rank correlation coefficients for non-normal distribution were utilized to remove redundant features. After that, a blending ensemble machine learning model were developed in training cohort. Area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA) were employed to evaluate the performance of the final model in testing cohort.ResultsThe fusion feature-based machine learning algorithm demonstrated excellent diagnostic performance in external validation dataset (AUC = 0.934, ACC = 0.905). Net benefits presented by DCA are higher than Bosniak-2019 version classification for stratifying patients with CRL to the appropriate surgery procedure.ConclusionsFusion feature-based classifier accurately distinguished malignant and benign CRLs which outperformed the Bosniak-2019 version classification and illustrated improved clinical decision-making utility.Key pointsBlending ensemble model achieved excellent diagnostic performance in the external validation dataset.Blending ensemble model exceeded the management performance based on the Bosniak classification.Histopathology criterion support ensured that blending ensemble model’s predictions were reliable.

Transplantation of neural stem cells (NSCs) is a potential strategy for the treatment of spinal cord transection (SCT). Here we investigated whether transplanted NSCs would improve motor function of rats with SCT and explored the underlying mechanism. First, the rats were divided into sham, SCT, and NSC groups. Rats in the SCT and NSC groups were all subjected to SCT in T10, and were administered with media and NSC transplantation into the lesion site, respectively. Immunohistochemistry was used to label Nestin-, TUNEL-, and NeuN-positive cells and reveal the expression and location of type I insulin-like growth factor receptor (IGF-1 R). Locomotor function of hind limbs was assessed by Basso, Beattie, Bresnahan (BBB) score and inclined plane test. The conduction velocity and amplitude of spinal nerve fibers were measured by electrophysiology and the anatomical changes were measured using magnetic resonance imaging. Moreover, expression of IGF-1 R was determined by real-time polymerase chain reaction and Western blotting. The results showed that NSCs could survive and differentiate into neurons in vitro and in vivo. SCT-induced deficits were reduced by NSC transplantation, including increase in NeuN-positive cells and decrease in apoptotic cells. Moreover, neurophysiological profiles indicated that the latent period was decreased and the peak-to-peak amplitude of spinal nerve fibers conduction was increased in transplanted rats, while morphological measures indicated that fractional anisotropy and the number of nerve fibers in the site of spinal cord injury were increased after NSC transplantation. In addition, mRNA and protein level of IGF-1 R were increased in the rostral segment in the NSC group, especially in neurons. Therefore, we concluded that NSC transplantation promotes motor function improvement of SCT, which might be associated with activated IGF-1 R, especially in the rostral site. All of the above suggests that this approach has potential for clinical treatment of spinal cord injury.

Objective: Due to recent developments and the wide application of percutaneous transforaminal discectomy (PTED), we herein compare it with microendoscopic discectomy (MED) and traditional open surgery (OD) through surgical indicators and postoperative outcomes to evaluate the advantages and disadvantages of minimally invasive surgery PTED. Methods: This systematic review and meta-analysis was conducted in line with PRISMA guidelines (PROSPERO2018: CRD42018094890). We searched four English and two Chinese databases from the date of their establishment to May 2022. Randomized controlled trials and case–control studies of PTED versus MED or PTED versus OD in the treatment of lumbar disc herniation were retrieved. Results: A total of 33 studies with 6467 cases were included. When comparing MED with PTED, the latter had less intraoperative blood loss, smaller incision, shorter postoperative bed times, shorter hospitalization times, better postoperative visual analogue scale (VAS) for low back pain, and postoperative dysfunction index (Oswestry Disability Index, ODI) and higher recurrence rates and revision rates. However, operation times, postoperative VAS leg scores and complications, and successful operation rates were similar in both groups. Comparison of PTED with OD revealed in the former less intraoperative blood loss and smaller incision, shorter postoperative bed times, shorter hospitalization times, shorter operation times, and higher recurrence rates and revision rates. Nonetheless, comprehensive postoperative VAS scores, VAS leg pain scores, VAS low back pain, ODI and incidence of complications, and successful operation rates were similar between the two groups. Conclusions: The therapeutic effect and safety of PTED, MED and OD in the treatment of lumbar disc herniation were comparable. PTED had obvious advantages in that it is minimally invasive, with rapid recovery after surgery, but its recurrence rates and revision rates were higher than MED and OD. Therefore, it is not possible to blindly consider replacing MED and OD with PTED.

Silk glands are specialized in the synthesis of several secretory proteins. Expression of genes encoding the silk proteins in Bombyx mori silk glands with strict territorial and developmental specificities is regulated by many transcription factors. In this study, we have characterized B. mori sage, which is closely related to sage in the fruitfly Drosophila melanogaster. It is termed Bmsage; it encodes transcription factor Bmsage, which belongs to the Mesp subfamily, containing a basic helix-loop-helix motif. Bmsage transcripts were detected specifically in the silk glands of B. mori larvae through RT-PCR analysis. Immunoblotting analysis confirmed the Bmsage protein existed exclusively in B. mori middle and posterior silk gland cells. Bmsage has a low level of expression in the 4th instar molting stages, which increases gradually in the 5th instar feeding stages and then declines from the wandering to the pupation stages. Quantitative PCR analysis suggested the expression level of Bmsage in a high silk strain was higher compared to a lower silk strain on day 3 of the larval 5th instar. Furthermore, far western blotting and co-immunoprecipitation assays showed the Bmsage protein interacted with the fork head transcription factor silk gland factor 1 (SGF1). An electrophoretic mobility shift assay showed the complex of Bmsage and SGF1 proteins bound to the A and B elements in the promoter of fibroin H-chain gene(fib-H), respectively. Luciferase reporter gene assays confirmed the complex of Bmsage and SGF1 proteins increased the expression of fib-H. Together, these results suggest Bmsage is involved in the regulation of the expression of fib-H by being together with SGF1 in B. mori PSG cells.

Complexin I (CPLX1), a presynaptic small molecule protein, forms SNARE complex in the central nervous system involved in the anchoring, pre-excitation, and fusion of axonal end vesicles. Abnormal expression of CPLX1 occurs in several neurodegenerative and psychiatric disorders that exhibit disrupted neurobehaviors. CPLX1 gene knockout induces severe ataxia and social behavioral deficits in mice, which has been poorly demonstrated. Here, to address the limitations of single-species models and to provide translational insights relevant to human diseases, we used CPLX1 knockout rats to further explore the function of the CPLX1 gene. The CRISPR/Cas9 gene editing system was adopted to generate CPLX1 knockout rats (CPLX1−/−). Then, we characterized the survival rate and behavioral phenotype of CPLX1−/− rats using behavioral analysis. To further explain this phenomenon, we performed blood glucose testing, Nissl staining, hematoxylin-eosin staining, and Golgi staining. We found that CPLX1−/− rats showed profound ataxia, dystonia, movement and exploratory deficits, and increased anxiety and sensory deficits but had normal cognitive function. Nevertheless, CPLX1−/− rats could swim without training. The abnormal histomorphology of the stomach and intestine were related to decreased weight and early death in these rats. Decreased dendritic branching was also found in spinal motor neurons in CPLX1−/− rats. In conclusion, CPLX1 gene knockout induced the abnormal histomorphology of the stomach and intestine and decreased dendritic branching in spinal motor neurons, causing different phenotypes between CPLX1−/− rats and mice, even though both of these phenotypes showed profound ataxia. These findings provide a new perspective for understanding the role of CPLX1.