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Traumatic brain injury (TBI) is a leading cause of disability and death. Thus, timely and effective secondary brain injury intervention is crucial, with potential to improve the prognosis of TBI. Oxidative stress contributes to post-traumatic secondary cognitive impairment, and the reduction of post-traumatic oxidative stress effectively enhances cognitive function. Phosphoglycerate-mutating enzyme 5 (PGAM5), a member of the phosphoglycerate transporter enzyme family, is upregulated in TBI and induces mitochondrial autophagy. This further exacerbates damage following TBI. The present study focused on the small molecule drug, LFHP-1c, which is a novel inhibitor of PGAM5. The present study used an in vivo mouse model incorporating a controlled cortical impact-induced TBI, to examine the impact of LFHP-1c on oxidative stress and cognitive function. The present study aimed to determine the impact of LFHP-1c on the PGAM5-Kelch-like ECH-associated protein 1 (KEAP1)- nuclear factor erythroid 2-related factor 2 (NRF2) ternary complex within the TBI context. Results of the present study indicated that LFHP-1c suppresses PGAM5 expression and inhibits the development of the PGAM5-KEAP1-NRF2 ternary complex, thereby promoting the release of NRF2 and KEAP1. This in turn promotes the entry of NRF2 into the nucleus following TBI, leading to increased expression of anti-oxidative stress downstream factors, such as heme oxygenase-1, glutathione peroxidase 1 and superoxide dismutase 1. In addition, LFHP-1c also released KEAP1, leading to mitochondrial Rho GTPase 2 degradation and reducing perinuclear aggregation of mitochondria in the cell, which reduced oxidative stress and ultimately improved cognitive function after TBI.

Abstract Background Perforated peptic ulcer (PPU) remains challenging surgically due to its high mortality, especially in older individuals. Computed tomography (CT)-measured skeletal muscle mass is a effective predictor of the surgical outcomes in older patients with abdominal emergencies. The purpose of this study is to assess whether a low CT-measured skeletal muscle mass can provide extra value in predicting PPU mortality. Methods This retrospective study enrolled older (aged ≥ 65 years) patients who underwent PPU surgery. Cross-sectional skeletal muscle areas and densities were measured by CT at L3 and patient-height adjusted to obtain the L3 skeletal muscle gauge (SMG). Thirty-day mortality was determined with univariate, multivariate and Kaplan–Meier analysis. Results From 2011 to 2016, 141 older patients were included; 54.8% had sarcopenia. They were further categorized into the PULP score ≤ 7 (n=64) or PULP score > 7 group (n=82). In the former, there was no significant difference in 30-day mortality between sarcopenic (2.9%) and nonsarcopenic patients (0%; p=1.000). However, in the PULP score > 7 group, sarcopenic patients had a significantly higher 30-day mortality (25.5% vs. 3.2%, p=0.009) and serious complication rate (37.3% vs. 12.9%, p=0.017) than nonsarcopenic patients. Multivariate analysis showed that sarcopenia was an independent risk factor for 30-day mortality in patients in the PULP score > 7 group (OR: 11.05, CI: 1.03-118.7). Conclusion CT scans can diagnose PPU and provide physiological measurements. Sarcopenia, defined as a low CT-measured SMG, provides extra value in predicting mortality in older PPU patients.

BackgroundMental health risks associated with the aftermath of the COVID-19 pandemic are often overlooked by the public. The aim of this study was to investigate the effects of the COVID-19 pandemic on depression and anxiety disorders in China.MethodsStudies were analyzed and extracted in accordance with the PRISMA 2020 flowchart. The studies were screened and extracted using electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov according to the predefined eligibility criteria. The Cochrane Review Manager software 5.3.1 was used for data analysis and the risk of bias assessment.ResultsAs of 2023, a total of 9,212,751 Chinese have been diagnosed with COVID-19 infection. A total of 913,036 participants in 44 studies were selected following the eligibility criteria, the statistical information of which was collected for meta-analysis. The pooled prevalence of depression and anxiety were 0.31 (95% CI: 0.28, 0.35; I2 = 100.0%, p

AIM: To investigate the clinical efficacy and safety of ultrasonic ciliary plasty(UCP)combined with injection of anti-vascular endothelial growth factor(VEGF)in the treatment of neovascular glaucoma(NVG).METHODS: A total of 30 NVG patients(30 eyes)admitted to the First Affiliated Hospital of Bengbu Medical College from September 2020 to September 2021 were selected. After admission, all the eyes of the patients were injected with anti-VEGF drug(ranibizumab). After surgery, 15 patients were randomly selected for UCP treatment(UCP group), and the other 15 patients received trabeculectomy(trabeculectomy group). During the 10mo postoperative follow-up, the decrease of intraocular pressure was compared between the two groups and the changes of the degree of ocular pain and the occurrence of related complications were evaluated at each follow-up visit.RESULTS: The intraocular pressure and pain degree of the UCP and trabeculectomy groups were significantly lower than those before operation, and the complication probability of the UCP group was less than that of the trabeculectomy group.CONCLUSION: With fewer complications and high safety, UCP combined with anti-VEGF injection can effectively control intraocular pressure and pain in NVG patients.

ABSTRACT Enterococcus faecalis is a hospital-associated opportunistic pathogen that can cause infections with high mortality, such as infective endocarditis. With an increasing occurrence of multidrug-resistant enterococci, there is a need for alternative strategies to treat enterococcal infections. We isolated a gentamicin-hypersusceptible E. faecalis strain from a patient with infective endocarditis that carried a mutation in the alpha-carbonic anhydrase (α-CA) and investigated how disruption of α-CA sensitized E. faecalis to killing with gentamicin. The gentamicin-hypersusceptible α-CA mutant strain showed increased intracellular gentamicin uptake in comparison to an isogenic strain encoding full-length, wild-type α-CA. We hypothesized that increased gentamicin uptake could be due to increased proton motive force (PMF), increased membrane permeability, or both. We observed increased intracellular ATP production in the α-CA mutant strain, suggesting increased PMF-driven gentamicin uptake contributed to the strain’s gentamicin susceptibility. We also analyzed the membrane permeability and fatty acid composition of isogenic wild-type and α-CA mutant strains and found that the mutant displayed a membrane composition that was consistent with increased membrane permeability. Finally, we observed that exposure to the FDA-approved α-CA inhibitor acetazolamide lowered the gentamicin MIC of eight genetically diverse E. faecalis strains with intact α-CA but did not change the MIC of the α-CA mutant strain. These results suggest that α-CA mutation or inhibition increases PMF and alters membrane permeability, leading to increased uptake of gentamicin into E. faecalis. This connection could be exploited clinically to provide new combination therapies for patients with enterococcal infections. IMPORTANCE Enterococcal infections can be difficult to treat, and new therapeutic approaches are needed. In studying an E. faecalis clinical strain from an infected patient, we found that the bacteria were rendered hypersusceptible to aminoglycoside antibiotics through a mutation that disrupted the α-CA. Our follow-on work suggested two different ways that α-CA disruption causes increased gentamicin accumulation in E. faecalis: increased proton motive force-powered uptake and increased membrane permeability. We also found that a mammalian CA inhibitor could sensitize a variety of E. faecalis strains to killing with gentamicin. Given that mammalian CA inhibitors are frequently used to treat conditions such as glaucoma, hypertension, and epilepsy, our findings suggest that these “off-the-shelf” inhibitors could also be useful partner antibiotics for the treatment of E. faecalis infections.

The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for “false-positive MRI diagnosis” included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.

Abstract Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.

Abstract Background Docetaxel (DTX) exhibits antitumor effects against breast cancer by stabilizing microtubules and increasing the accumulation of reactive oxygen species (ROS). DTX extravasation during infusion often causes skin injury. The present study aimed to investigate the effects and mechanisms of icaritin (ICT) on DTX‐induced skin injury. Methods The effects of ICT on the viability and apoptosis of HaCaT cells were measured by SRB assay and flow cytometry, respectively. Endogenous LC3 puncta and microtubules were determined by immunofluorescence. The number of mitochondria was measured by MitoTracker orange staining. ROS were determined by dihydroethidium staining. The expression of markers of ROS and autophagy were measured by western blotting. Chloroquine, compound D, and tamoxifen were employed as the inhibitor for autophagy and AMPK, estrogen receptors (ERs) modulator, respectively. Results DTX inhibited the viability and decreased apoptosis of HaCaT cells, which can be rescued by ICT. ICT decreased microtubule bundles, increased the number of mitochondria, and attenuated ROS of HaCaT cells induced by DTX. ICT blocks autophagy and the autophagic flux. Compound C or tamoxifen diminished the protection effects of ICT on DTX‐treated HaCaT cells. Conclusion ICT alleviates DTX‐induced skin injury by suppressing ROS, reducing microtubule bundles, and blocking autophagy via ERs. Our study indicated that ICT may be a potential candidate for DTX‐induced skin injury.

IntroductionBitter peptides are short peptides with potential medical applications. The huge potential behind its bitter taste remains to be tapped. To better explore the value of bitter peptides in practice, we need a more effective classification method for identifying bitter peptides.MethodsIn this study, we developed a Random forest (RF)-based model, called Bitter-RF, using sequence information of the bitter peptide. Bitter-RF covers more comprehensive and extensive information by integrating 10 features extracted from the bitter peptides and achieves better results than the latest generation model on independent validation set.ResultsThe proposed model can improve the accurate classification of bitter peptides (AUROC = 0.98 on independent set test) and enrich the practical application of RF method in protein classification tasks which has not been used to build a prediction model for bitter peptides.DiscussionWe hope the Bitter-RF could provide more conveniences to scholars for bitter peptide research.

The spiking neural network (SNN), closely inspired by the human brain, is one of the most powerful platforms to enable highly efficient, low cost, and robust neuromorphic computations in hardware using traditional or emerging electron devices within an integrated system. In the hardware implementation, the building of artificial spiking neurons is fundamental for constructing the whole system. However, with the slowing down of Moore's Law, the traditional complementary metal-oxide-semiconductor (CMOS) technology is gradually fading and is unable to meet the growing needs of neuromorphic computing. Besides, the existing artificial neuron circuits are complex owing to the limited bio-plausibility of CMOS devices. Memristors with volatile threshold switching (TS) behaviors and rich dynamics are promising candidates to emulate the biological spiking neurons beyond the CMOS technology and build high-efficient neuromorphic systems. Herein, the state-of-the-art about the fundamental knowledge of SNNs is reviewed. Moreover, we review the implementation of TS memristor-based neurons, and their systems, and point out the challenges that should be further considered from devices to circuits in the system demonstrations. We hope that this review could provide clues and be helpful for the future development of neuromorphic computing with memristors.

Local anesthesia (LA) is the most important pain management process in oral and maxillofacial surgery. Safe and effective LA not only enable patients to obtain high-quality treatment, but also relieve the anxiety of patients when they come to the clinic. The choices of local anesthetic and injection methods determine the success of LA to a great extent. At present, in most countries or regions, common local anesthetics used in oral and maxillofacial surgery belong to amides and they are injected into patients' body mainly through block or infiltration anesthesia. In addition, the operators' technique level, patient's subjective psychology and anatomical variation of maxillofacial structure also have a strong influence on LA in dental clinic. Due to the existence of above factors, the worldwide success rates of LA in oral and maxillofacial surgery is very different. There are no specific LA methods that ensure 100% successful LA rates. Fortunately, the development of new local anesthetic and injection technology are providing us with new ideas to solve this problem. This review mainly report the new research progress on LA in oral and maxillofacial surgery in recent decades and help clinicians with dental LA operation.

Bayer filter color cameras are more and more widely used in the field of aerospace remote sensing, but the Bayer filter causes great degradation in image quality; therefore, obtaining a means of achieving the high-precision measurement of the modulation transfer function (MTF) of Bayer filter color cameras is an urgent problem. In order to solve this problem, this paper develops a slanted-edge method via three steps: the detection of the slanted edge, the acquisition and processing of the edge spread function (ESF), and the acquisition and processing of the line spread function (LSF). A combination of the Canny operator and Hough transform is proposed for the detection of the slanted edge, which improves the fitting accuracy and anti-interference ability of the algorithm. Further, the Canny operator is improved by constructing an adaptive filter function and introducing the Otsu method, which can more effectively smooth the image and remove its false edges. A method of processing ESF data by combining cubic spline interpolation and Savitzky–Golay (SG) filtering is proposed, which reduces the effects of noise and the non-uniform sampling of ESF on MTF. A method of LSF processing using Gaussian function fitting is proposed to further reduce the effect of noise on MTF. The improved algorithm is verified by the MTF measurement test applied to a specific type of Bayer filter color space camera. The simulation and test results show that the improved slanted-edge method discussed in this paper has greater precision and a better anti-interference ability, and it can effectively solve the difficult problem associated with MTF detection in Bayer filter color space cameras.

As a beneficial supplement to radio frequency communication, Visible Light Communication (VLC) can provide highspeed, ultra-low delay, green, low-cost, safe and reliable communication services. However, limited coverage range has become the bottleneck of long distance and reliable communication in VLC system. Since the coverage range of VLC is limited, an effective method is proposed to use relay technology in VLC system. The paper starts from the functional characteristics of relay technology, and analyzes the relay system model. Then we give a review on several key technologies of relay-assisted VLC, including the application scenario, network mode, transfer agreement, modulation mode, working mode and non-orthogonal multiple access. The reliable performance, safety and energy efficiency with the corresponding key technologies are analyzed. Finally, we point out a research emphasis and direction in VLC by adopting the heterogeneous network, non-orthogonal multiple access, multi-input and multi-output, full-duplex mode multiple and relays collaboration for the next generation communication network.

Background: Much attention has been focused on environmental risk factors and their roles in eczema development. In this regard, the specific eczema risk factors in Taiwan were relatively unknown. As such, this study investigated the common indoor risk factors present in Taiwanese households. Aims: To discuss the effects of several indoor risk factors on the prevalence of atopic eczema in Taiwan. Materials and Methods: A cross-sectional, population-based study was performed in Kaohsiung, Taiwan, using both survey investigation and fungal culturing. A total of 998 participants were enrolled in the survey, with 513 participants selected for fungal culture. Risks of atopic eczema were calculated as odds ratios for various risk factors using logistic regression. The correlation between potential risk factors and the fungal level was analyzed with linear regression. Results: Pet and house plants have an adjusted odds ratio of 1.434 (95% CL: 1.011–2.033) and 1.820 (95% CL: 1.229-2.696), respectively. Additionally, smoking was shown to possess an odds ratio of 1.461 (95% CL: 1.064-2.006). Wood wall has an adjusted odds ratio of 2.143 (95% CL: 1.235-3.658). Frequent bedroom shower use (β = 0.254) and hours of opened windows (β = 0.106) have shown significant positive associations with indoor fungal level. Conclusion: Pets, house plants, and smoking were concluded to be major risk factors for atopic eczema. Wood wall remained controversial due to its limited sample size and possible confounders. Bedroom shower and window-opening have been shown to increase mold growth, but the lack of association with eczema suggested other allergens besides mold to be the primary eczema trigger.

Skeletal muscle injuries have bothered doctors and caused great burdens to the public medical insurance system for a long time. Once injured, skeletal muscles usually go through the processes of inflammation, repairing and remodeling. If repairing and remodeling stages are out of balance, scars will be formed to replace injured skeletal muscles. At present, clinicians usually use conventional methods to restore the injured skeletal muscles, such as flap transplantation. However, flap transplantation sometimes needs to sacrifice healthy autologous tissues and will bring extra harm to patients. In recent years, stem cells-based tissue engineering provides us new treatment ideas for skeletal muscle injuries. Stem cells are cells with multiple differentiation potential and have ability to differentiate into adult cells under special condition. Skeletal muscle tissues also have stem cells, called satellite cells, but they are in small amount and new muscle fibers that derived from them may not be enough to replace injured fibers. Bone marrow mesenchymal stem cells (BM-MSCs) could promote musculoskeletal tissue regeneration and activate the myogenic differentiation of satellite cells. Biomaterial is another important factor to promote tissue regeneration and greatly enhance physiological activities of stem cells in vivo. The combined use of stem cells and biomaterials will gradually become a mainstream to restore injured skeletal muscles in the future. This review article mainly focuses on the review of research about the application of BM-MSCs and several major biomaterials in skeletal muscle regeneration over the past decades.

An organocatalytic asymmetric construction of hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted allene scaffolds bearing both axial chirality and central chirality has been established via a cascade 1,8-addition/dearomatization-cyclization reaction of para-aminophenyl propargylic alcohols with tryptamines in the presence of chiral phosphoric acid (CPA), thus affording a wide range of such tetrasubstituted allenes bearing multiple chiral elements in generally good yields (up to 94%) with high diastereo- and enantioselectivities (up to 95:5 dr, 95% ee). In addition, the evaluation on the cytotoxicity of some selected products indicated that this class of chiral tetrasubstituted allenes could inhibit the growth of the pancreatic cancer cells to some extent. This work not only solved the challenging issues in enantioselective construction of tetrasubstituted allenes via alkynyl (aza)-para-quinone methides, but also represents the first example of using alkyne derivatives as electrophiles in organocatalytic asymmetric dearomatizations of tryptamines.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps growing recently.Purpose: To investigate the effects and mechanisms of naringenin (NAR) on NAFLD.Methods: High-fat diet (HFD)-induced NAFLD rats were orally administered with NAR at 10, 30, and 90 mg/kg for 2 weeks. The serum level of triglyceride (TG), total cholesterol (TC), glutamic-oxaloacetic transaminase (AST), and glutamic-pyruvic transaminase (ALT) was measured. The hepatic histology was detected by H&E and oil red O staining. L02 and Huh-7 cells were induced by sodium oleate to establish a NAFLD cell model. The effects of NAR on lipid accumulation were detected by oil red O staining. The glucose uptake and ATP content of 3T3-L1 adipocytes and C2C12 myotubes were measured. The expression of proteins of the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes was assessed by Western blotting. The mitochondrial biogenesis of 3T3-L1 adipocytes and C2C12 myotubes was measured by mitotracker orange staining and Western blotting. The biomarkers of autophagy were detected by Western blotting and immunofluorescence. The binding of NAR to AMPKγ1 was analyzed by molecular docking. Chloroquine and compound C were employed to block autophagic flux and AMPK, respectively.Results: NAR alleviated HFD-induced NAFLD in rats at 10, 30, and 90 mg/kg. NAR attenuated lipid accumulation in L02 and Huh-7 cells at 0.7, 2.2, 6.7, and 20 μM. NAR increased glucose uptake, decreased the ATP content, activated the CaMKKβ/AMPK/ACC pathway, and enhanced the mitochondrial biogenesis in 3T3-L1 adipocytes and C2C12 myotubes. NAR increased autophagy and promoted the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts, while it inhibited autophagy in NAFLD rats, 3T3-L1 adipocytes, and C2C12 myotubes. Molecular docking showed that NAR binds to AMPKγ1. Compound C blocked effects of NAR on lipid accumulation and autophagy in L02 cells.Conclusion: NAR alleviates NAFLD by increasing energy expenditure and regulating autophagy via activating AMPK directly and indirectly. The direct binding of NAR and AMPKγ1 needs further validation.

Nerve injury is a critical problem in the clinic. Nerve injury causes serious clinic issues including pain and dysfunctions for patients. The disconnection between damaged neural fibers and muscles will result in muscle atrophy in a few weeks if no treatment is applied. Moreover, scientists have discovered that nerve injury can affect the osteogenic differentiation of skeletal stem cells (SSCs) and the fracture repairing. In plastic surgery, muscle atrophy and bone fracture after nerve injury have plagued clinicians for many years. How to promote neural regeneration is the core issue of research in the recent years. Without obvious effects of traditional neurosurgical treatments, research on stem cells in the past 10 years has provided a new therapeutic strategy for us to address this problem. Adipose stem cells (ASCs) are a kind of mesenchymal stem cells that have differentiation potential in adipose tissue. In the recent years, ASCs have become the focus of regenerative medicine. They play a pivotal role in tissue regeneration engineering. As a type of stem cell, ASCs are becoming popular for neuroregenerative medicine due to their advantages and characteristics. In the various diseases of the nervous system, ASCs are gradually applied to treat the related diseases. This review article focuses on the mechanism and clinical application of ASCs in nerve regeneration as well as the related research on ASCs over the past decades.

This article discusses a study on the use of esophageal balloon catheters to measure respiratory effort and mechanics in patients receiving mechanical ventilation. The researchers used a system identification approach to improve the accuracy of these measurements. They conducted tests in a controlled setting and with patient data, and found that correcting the dynamic response of the balloon catheter improved the accuracy of resistance and compliance estimates. The study acknowledges limitations and suggests further investigation, but concludes that using esophageal pressure measurements can improve ventilator settings and decision-making. The data from the study are available upon request. [Extracted from the article]