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Abstract Background Venous thromboembolism (VTE) is a common complication after hip arthroplasty. Here, we investigated the clinical efficacy and safety of prophylactic aspirin vs. conventional therapy in hip arthroplasty for femoral neck fracture. Methods Patients who underwent total hip arthroplasty and hemiarthroplasty for femoral neck fractures between April 2021 and April 2024 were prospectively enrolled. Group A received oral aspirin (100 mg, once daily) as VTE prophylaxis; Group LR received low-molecular-weight heparin (4,250 U, once daily) sequentially followed by rivaroxaban (10 mg, once daily). The patients were followed up for 90 days postoperatively. Safety and efficacy were comprehensively evaluated based on postoperative VTE incidence, laboratory blood tests, bleeding events, and other complications. Results Group A was noninferior to Group LR in preventing VTE (incidence rates of 11.6% and 10.1%, respectively, with a rate difference of 1.5%, 95% CI: 0.7–2.3%, P for non-inferiority test = 0.017). There was no significant difference between the groups in the incidence of bleeding events (3.3 vs. 8.4%; P = 0.092). Furthermore, the rates of other complications did not differ significantly between groups. Conclusion In patients undergoing hip arthroplasty for femoral neck fractures, the efficacy and safety of oral aspirin for preventing VTE was similar to that of low-molecular-weight heparin followed by rivaroxaban.

Objectives: To investigate the preventive effect of intraarticularly administered vancomycin on acute postoperative periprosthetic joint infection (PJI) in total joint arthroplasty (TJA). Methods: Consecutive patients who underwent unilateral primary TJA were prospectively enrolled. The patients were divided into vancomycin group and control group according to whether 1 g of vancomycin powder suspended in 30 ml normal saline was intraarticularly administered after arthrotomy closure. Acute postoperative PJI and aseptic wound complication were evaluated within 3 months postoperatively. Vancomycin-associated toxicity including acute renal failure, ototoxicity and anaphylaxis was also evaluated. Results: In terms of demographic parameters and comorbidities, no significant difference was found between the two groups. Intra-articular vancomycin significantly lowered the risk of acute postoperative PJI after primary TJA (P = 0.015) and primary total knee arthroplasty (P = 0.031). However, for patients who underwent total hip arthroplasty, the PJI rate was comparable between the two groups. Overall, the risk of aseptic wound complication between the two groups was also similar. Vancomycin-associated acute renal injury, ototoxicity, or anaphylaxis was not observed. Conclusions: Intra-articular injection of 1 g of vancomycin suspension after arthrotomy closure during TJA lowered the risk of acute postoperative PJI without increasing the risk of aseptic wound complication and vancomycin-associated systemic toxicity.

Phosphaturic mesenchymal tumors (PMT) are rare and distinctive tumors that typically result in paraneoplastic syndrome known as tumor-induced osteomalacia (TIO). We report a case of bilateral osteoporotic femoral neck fracture caused by PMT. PMT was surgically resected, followed by sequential treatment of bilateral femoral neck fractures with total hip arthroplasty (THA). A 49-year-old perimenopausal woman experienced consistent bone pain with limb weakness persisting for over 2 years. Initially, she was diagnosed with early osteonecrosis of the femoral head and received nonsurgical treatment. However, from 2020 to 2022, her pain extended to the bilateral shoulders and knees with increased intensity. She had no positive family history or any other genetic diseases, and her menstrual cycles were regular. Physical examination revealed tenderness at the midpoints of the bilateral groin and restricted bilateral hip range of motion, with grade 3/5 muscle strength in both lower extremities. Laboratory findings revealed moderate anemia (hemoglobin 66 g/L), leukopenia (2.70 × 109/L), neutropenia (1.28 × 109/L), hypophosphatemia (0.36 mmol/L), high alkaline phosphatase activity (308.00 U/L), and normal serum calcium (2.22 mmol/L). After surgery, additional examinations were performed to explore the cause of hypophosphatemic osteomalacia. After definitive diagnosis, the patient underwent tumor resection via T11 laminectomy on August 6, 2022. Six months after the second THA, the patient regained normal gait with satisfactory hip movement function without recurrence of PMT-associated osteomalacia or prosthesis loosening. By providing detailed clinical data and a diagnostic and treatment approach, we aimed to improve the clinical understanding of femoral neck fractures caused by TIO.

ObjectivesTo investigate the efficacy of serum protein electrophoresis (SPE) in the diagnosis of periprosthetic joint infection (PJI) after hip and knee arthroplasty.MethodsThe medical records of patients undergoing hip and knee arthroplasty at a class A tertiary hospital between August 2013 and January 2021 were retrospectively investigated. A total of 179 patients were included and divided into two groups: 66 patients in the PJI group and 113 patients in the aseptic loosening (AL) group. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, Fibrinogen, Serum albumin and the proportion of serum protein in SPE were compared between the two groups. The diagnostic sensitivity and specificity were determined using the receiver operating characteristic (ROC) curve, and the diagnostic value was compared using the area under the ROC curve (AUC).ResultsThere was no significant difference in age, sex and body mass index (BMI) between PJI group and AL group (P>0.05), but there was significant difference in the ratio of hip to knee (X2 = 22.043, P

The low-permeability characteristic of sandstone-type uranium deposits has become the key geological bottleneck during the in-situ leaching mining, seriously restricting the development and utilization of uranium resources in China. At present, the blasting-enhanced permeability (BEP) and acidizing-enhanced permeability (AEP) are confirmed to be mainstream approaches to enhance the reservoir permeability of low-permeability sandstone-type uranium deposit (LPSUD). To clarify the synergistic effect of BEP and AEP, the acid-rock reaction and dynamic impact experiments were conducted, aiming to study the effect of chemical reactions on pore structure, dynamic mechanical properties and failure pattern of sandstone. Results show that with the increasing acid-rock reaction time, the total pore volume of samples is promoted largely and exhibits obvious chemical damage. The change of pore volume depends on the pore size, the 100–1000 nm and 1000–10000 nm pores are more susceptible to acid-rock reactions. The dynamic peak strength and the dynamic elastic modulus are decreased and the dynamic peak strain and strain rate are increased when lengthening the acid-rock reaction time, whose evolution laws can be fitted by the logistic expression, the linear expression and the exponential expression, respectively. The acid-rock reactions also have an influence on the fracture development of samples after the dynamic impact. The damaged fractures on the end faces of samples grow from the isolated short fracture, the isolated long fracture to the fracture network, and the damaged fractures on the sides of samples develop from the non-penetration fractures, penetration fractures to the multi-branch fractures. This study clarifies the physical and chemical combined damage mechanism, demonstrates the potential of reservoir stimulation by uniting the BEP and the AEP, and provides a theoretical reference for the reservoir stimulation of LPSUD.

Introduction: Total knee arthroplasty (TKA) has been recognized as the most efficacious surgical intervention for individuals suffering from advanced arthritis; however, there is ongoing debate on the technical details of the procedure. It remains unknown whether preservation of the posterior cruciate ligament (PCL) significantly affects the mid-to long-term performance of ADVANCE® medial-pivotal (AMP) knee implants to enhance patient satisfaction. The hypothesis of this study was to investigate whether the preservation of the PCL has a substantial impact on the functional outcomes of medial pivot (MP) implants in patients undergoing TKA. Therefore, this study aimed to compare the midterm clinical and radiographic outcomes of cruciate-retaining (CR) and cruciate-substituting (CS) TKA using MP prostheses. Methods: We included 376 consecutive patients who underwent unilateral TKA between January 2011 and April 2014. Follow-up evaluations were conducted in April 2021. After propensity score matching analysis, clinical and radiological outcomes and complication rates were compared between patients in the CR and CS groups. Results: The postoperative outcomes in the two groups significantly improved the preoperative conditions of the patients (all p > 0.05). The postoperative outcomes (WOMAC score, p = 0.517; KSS, p = 0.107; KSFS, p = 0.240; ROM, p = 0.795; FJS, p = 0.822) and radiographic outcomes (preoperative FTA, p = 0.997; postoperative FTA, p = 0.646; aLDFA, p = 0.094; aMPTA, p = 0.970; PTS, p = 0.243) were comparable between the two groups. The complication and revision rates between the groups were not statistically significant (p = 0.34). The Kaplan–Meier cumulative survival of patients in the CRTKA and CSTKA groups was 100 % and 98.6 %, respectively. Conclusions: This study supports the hypothesis that when MP prostheses are used, both CR and CS procedures achieve equally good mid-to long-term clinical and radiographic outcomes and complication rates. These findings suggest that PCL preservation may not significantly affect the overall performance of MP implants in patients undergoing TKA.

Abstract Purpose To compare the effect of vancomycin presoak treatment of grafts during anterior cruciate ligament reconstruction on the incidence of postoperative infection or septic arthritis. Methods Studies published before May 3, 2022 investigating vancomycin presoak of grafts during anterior cruciate ligament reconstruction were searched in the PubMed and Cochrane Central Register of Controlled Trials. Studies were screened, and data on the incidence of postoperative infection or septic arthritis were extracted and included in the analysis. Results Thirteen studies were included for analysis after search screening, yielding a total of 31,150 participants for analysis, of whom 11,437 received graft vancomycin presoak treatment, and 19,713 did not receive treatment. Participants who received vancomycin treatment had significantly lower infection rates (0.09% versus 0.74%; OR 0.17; 95% CI 0.10, 0.30; P

PurposeTo assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients with osteoporosis.MethodsPubMed was searched for studies published until January 28, 2023, that investigated the clinical efficacy and bone turnover marker changes of denosumab and romosozumab in the treatment of osteoporosis, with a minimum follow-up of 3 months in each study. Studies were screened, and data on changes in bone mineral density (BMD), P1NP, and TRACP-5b levels after treatment were extracted and included in the analysis.ResultsSix studies were analyzed. At 3 months after treatment, the romosozumab group showed greater changes in lumbar BMD and bone turnover markers. BMD of total hip and femoral neck was relatively delayed. Beginning at 6 to 12 months, romosozumab showed greater changes in bone mineral density and markers of bone turnover.ConclusionBoth romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023395034.

Abstract Background The postoperative clinical outcomes has been extensively demonstrated to correlate with the coronal alignment after total knee arthroplasty (TKA). However, in different studies, either the hip-knee-ankle angle (HKA) on a full-length radiograph or the femorotibial angle (FTA) on a short knee film was used to categorize the postoperative coronal alignment. Meanwhile, several different FTA ranges were regarded as neutral alignment in different studies. As a result, it is still unknown that how FTA on short knee films and HKA related to each other. The FTA may be able to become an accurate proxy of HKA to predict the coronal alignment. The purpose of this study was to explore the correlation between the FTA and the HKA after TKA and to find the most accurate FTA range. Methods About 223 patients were included in this study and standard weight-bearing short knee films as well as full-length radiographs were acquired. The pre- and postoperative FTA, as well as the postoperative anatomical lateral distal femoral angle (aLDFA) and anatomical medial proximal tibial angle (aMPTA) were measured on short knee films by two orthopedic surgeons independently. On full-length films, the pre- and postoperative FTA, the pre- and postoperative HKA, as well as the postoperative mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were also recorded by two other surgeons independently. Pearson correlation analysis was performed to compare FTA and HKA, aMTPA and mMTPA, aLDFA and mLDFA, respectively. Results The postoperative FTA and HKA had a good correlation (r = 0.86). The agreements were reached 82.7%, 71.0%, and 68.2% of all patients using three previously reported FTA ranges. When analyzing the independent alignment of the tibial tray and the femoral component, 84.1% and 57.9% of all patients was reached an agreement on the classification. Conclusions On most occasions, the consistence between the FTA and HKA in assessing the coronal limb alignment of the lower extremity and the tibial component is satisfactory. However, the postoperative full-length film is still needed to evaluate accurately the coronal alignment of the femoral component.

Guaranteeing CO2 injectivity has been the precondition for implementing the CO2-enhanced coalbed methane recovery (CO2-ECBM), however, it dramatically decreases during the CO2 injection process because it is influenced by the dynamic change of the anisotropic permeability of coal. To reveal and evaluate the CO2 injectivity of coal, the anisotropic permeability test and the CO2 injectivity simulation test were first conducted, then the corresponding numerical models were established and verified by the experimental data. The results show that the permeability of coal in parallel face cleat direction is the largest, followed by the permeability of coal in parallel butt cleat direction and that in vertical bedding direction is the minimum. The peak value of the instantaneous injectivity rate is enhanced and the injection time is prolonged with the increase of the CO2 injection pressure. The total CO2 injectivity rate is nonlinearly increased from 13.61 to 311.87 cm2/MPa min when the CO2 injection pressure raises from 2 to 10 MPa. The anisotropic permeability model is appropriate to describe the dynamic evolution of permeability under different boundary conditions, the CO2 injectivity prediction model can be used to evaluate the CO2 injectivity during the CO2 injection process. Increasing the CO2 injection pressure may temporarily promote CO2 injectivity, while the CO2 injection increment is limited. The CO2 fracturing by phase transition may be an available reservoir stimulation method for enhancing the CO2 injection and should be focused on in the future.

Osteoarthritis (OA) and Parkinson’s disease (PD) are on the rise and greatly impact the quality of individuals’ lives. Although accumulating evidence indicates a relationship between OA and PD, the particular interactions connecting the two diseases have not been thoroughly examined. Therefore, this study explored the association through genetic characterization and functional enrichment. Four datasets (GSE55235, GSE12021, GSE7621, and GSE42966) were chosen for assessment and validation from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was implemented to determine the most relevant genes for clinical features. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to explore the biological processes of common genes, and to display the interrelationships between common genes, the STRING database and the application Molecular Complex Detection Algorithm (MCODE) of Cytoscape software were leveraged to get hub genes. By intersecting the common genes with the differentially expressed genes (DEGs) acquired from GSE12021 and GSE42966, the hub genes were identified. Finally, we validated the diagnostic efficacy of hub genes and explored their correlation with 22 immune infiltrating cells. As a consequence, we discovered 71 common genes, most of which were functionally enriched in antigen processing and presentation, mitochondrial translation, the mRNA surveillance pathway, and nucleocytoplasmic transport. Furthermore, WDR43 was found by intersecting eight hub genes with 28 DEGs from the two validation datasets. Receiver Operating Characteristic (ROC) implied the diagnostic role of WDR43 in OA and PD. Immune infiltration research revealed that T-cell regulatory (Tregs), monocytes, and mast cells resting were associated with the pathogenesis of OA and PD. WDR43 may provide key insights into the relationship between OA and PD.

BackgroundChanges in the neutrophil-lymphocyte ratio (NLR) has been reported to be associated with epilepsy. Here we aim to investigate the correlation of temporal changes of NLR level with seizure severity and the follow-up seizure attacks in patients with epilepsy (PWE).MethodsWe performed a retrospective analysis of the laboratory data including leukocyte count and NLR within 24 h of acute seizure and during the follow-up period of 5–14 days after acute seizure (NLR1, NLR2, respectively) in 115 PWE, and 98 healthy individuals were included as controls in this study. The correlation of laboratory data with seizure types, etiology of epilepsy, anti-seizure drugs (ASDs), seizure severity, and the follow-up seizure attacks in PWE was studied.ResultsLeukocyte count (P < 0.001) and NLR level (P < 0.001) were found significantly different between PWE and controls. On the other hand, a multivariable logistic regression analysis showed that NLR1 level (OR = 2.992, P = 0.001) and admission leukocyte (OR = 2.307, P = 0.002) were both independently associated with acute epileptic seizures. Especially, higher NLR1 level was significantly associated with status epileptics (P = 0.013) and recurrent seizures after admission (P < 0.001). Furthermore, the multivariable logistic regression analysis indicated that higher NLR1 was a predictor for the tendency of the following recurrent seizure attacks (OR = 1.144, P = 0.002). NLR2 was inversely correlated with ASDs taken (P = 0.011). Levels of NLR1 (r = 0.441, P < 0.001) and NLR2 (r = 0.241, P = 0.009) were both positively correlated with seizure severity.ConclusionsSeizures were correlated with the alterations of systemic inflammation reflected by leukocyte and NLR. NLR1 and admission leukocyte were both independently associated with acute epileptic seizures. Higher NLR1 was associated with status epilepticus and independently predicted the tendency of the following epileptic seizures. NLR2 was significantly associated with ASDs taken. Besides, NLR may be used as a biomarker for seizure severity.

A nonlinear stiffness modeling method for collaborative robots（Cobots） is proposed， which is combine the finite element analysis method （FEA） with the virtual joint method （VJM）. This modeling method not only includes the linear and coupled stiffness of the link and joint modules， but also takes into account the nonlinear stiffness of transmission systems of robot， the change rate of Jacobian matrix under loads and the influence of the changes of poses are caused by the load and deadweight on nonlinear stiffness of robot. The structure stiffness matrices of link modules and joint modules are obtained by finite element substructure method. Combined with the nonlinear stiffness model of the transmission system， the nonlinear comprehensive stiffness model of each robot module is established. The static equilibrium pose and the force of each module under external force and self-weight condition are calculated by numerical calculation method. Based on the VJM， a nonlinear stiffness model of robot is built， and the validity of this method is proved by nonlinear finite element simulation.

With the requirement of pose repeatability of robots， searching the optimal arrangement scheme of random motion accuracy of joints can make robot design more reasonable and reduce the development cost of robots. Firstly， based on the analysis of pose repeatability of robots， a mathematical model of pose repeatability is established. The model includes position repeatability and orientation repeatability of robots. Then， with the accuracy optimization evaluation function of maximization of joint motion error， the optimal synthesis of pose repeatability for collaborative robot KUKA iiwa 7 is performed. And the optimal arrangement scheme of random motion accuracy of joints can be obtained. Finally， the method is verified by carrying the pose repeatability test of KUKA iiwa 7， and the results of accuracy design by this method can make robot design more reasonable.

BackgroundGeneralized tonic–clonic seizures (GTCS) are associated with significant disability and sudden unexpected death when they cannot be controlled. We aimed to explore the underlying neural substrate of the different responses to antiseizure drugs between the seizure-free (SF) and non-seizure-free (NSF) patients with GTCS through the amplitude of low-frequency fluctuation (ALFF) method.MethodsWe calculated ALFF among the SF group, NSF group, and healthy controls (HCs) by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data. One-way ANOVA was used to compare the ALFF of the three groups, and post-hoc analysis was done at the same time. Pearson's correlation analysis between ALFF in the discrepant brain areas and the clinical characteristics (disease course and age of onset of GTCS) was calculated after then.ResultsA significant group effect was found in the right fusiform gyrus (R.FG), left fusiform gyrus (L.FG), left middle occipital gyrus (L.MOG), right inferior frontal gyrus (R.IFG), right precentral gyrus (R.PreG), right postcentral gyrus (R.PostG), and left calcarine sulcus (L.CS). The SF and NSF groups both showed increased ALFF in all discrepant brain areas compared to HCs except the R.IFG in the NSF group. Significantly higher ALFF in the bilateral FG and lower ALFF in the R.IFG were found in the NSF group compared to the SF group.ConclusionsHigher ALFF in the bilateral FG were found in the NSF group compared to the SF and HC groups. Our findings indicate that abnormal brain activity in the FG may be one potential neural substrate to interpret the failure of seizure control in patients with GTCS.

Perovskite materials have high potential for the renewable energy sources such as solar PV cells, fuel cells, etc. Different structural distortions such as crystal structure and lattice parameters have a critical impact on the determination of the perovskite’s structure strength, stability, and overall performance of the materials in the applications. To improve the perovskite performance and accelerate the prediction of different structural distortions, few ML models have been established to predict the type of crystal structures and their lattice parameters using the basic atom characteristics of the perovskite materials. In this work, different ML models such as random forest (RF), support vector machine (SVM), neural network (NN), and genetic algorithm (GA) supported neural network (GA-NN) have been established, whereas support vector regression (SVR) and genetic algorithm-supported support vector regression (GA-SVR) models have been assessed for the prediction of the lattice parameters. The prediction model accuracy for the crystal structure classification is almost 88% in average for GA-NN whereas for the lattice constants regression model GA-SVR model gives ~95% in average which can be further improved by accumulating more robust datasets into the database. These ML models can be used as an alternative process to accelerate the development of finding out new perovskite material by providing valuable insight for the behaviours of the perovskite materials.

Using first-principles calculations, a new type of the full-Heusler alloy, namly, Ag2ScGe, with XA configuration, is proposed. The unit cell of the Ag2ScGe alloy consists of 16 atoms, and it is found that there may be two different phases: XA and L21. To determine the stable configuration of the Ag2ScGe alloy, we calculated the formation energy, energy curve, and phonon spectrum of the two configurations of the Ag2ScGe alloy and finally determined the new stable structure, i.e. the XA configuration of the Ag2ScGe alloy. Calculations of the mechanical properties and electronic properties show that this new structure exhibits the properties of a ductile and metallic material with elastic anisotropy. In addition, by calculating the optical properties of this new alloy, it is concluded that Ag2ScGe alloy is a good absorber in the visible light region.

With the rapid growth of vehicle population and vehicle miles traveled, automobile emission has become a severe issue in the metropolitan cities of China. There are policies that concentrate on the management of emission sources. However, improving the operation of the transportation system through apps on mobile devices, especially navigation apps, may have a unique role in promoting urban air quality. Real-time traveler information can not only help travelers avoid traffic congestion, but also advise them to adjust their departure time, mode, or route, or even to cancel trips. Will such changes in personal travel patterns have a significant impact in decreasing emissions? If so, to what extent will they impact urban air quality? The aim of this study is to determine how urban traffic emission is affected by the use of navigation apps. With this work, we attempt to answer the question of whether the real-time traffic information provided by navigation apps can help to improve urban air quality. Some of these findings may provide references for the formulation of urban traffic and environmental policies. Keywords: Real-time traffic information, Mobile devices, Environmental benefits, Agent-based model

Due to the raising economy development of Shenzhen, environmental problems brought by road transport have become more serious. Promoting liquefied natural gas vehicle in the road freight is a key to reduce emissions, change the direction for road freight development, and build a resource-saving society. This article studies the application of liquefied natural gas vehicle in Shenzhen in-depth through official data sets, field investigation, expert consultation, and so on. Economic benefit analysis shows that liquefied natural gas vehicle has the advantage of saving considerable fuel costs for enterprises. Moreover, the Monte-Carlo method is used to evaluate the economic benefits considering a lot of factors. The economic analysis shows that the liquefied natural gas vehicle is more affordable than the diesel vehicle. Finally, the current issues of liquefied natural gas vehicles on the promotion are discussed and some advices are proposed to improve air quality and reduce emissions.

The specialized equipment utilized in long-line tunnel engineering is evolving towards large-scale,multifunctional, and complex orientations. The vibration caused by the high-frequency units during regular operation is supported by the foundation of the units, and the magnitude of vibration and the operating frequency fluctuate in different engineering contexts, leading to variations in the dynamic response of the foundation. The high-frequency units yield significantly diverse outcomes under different startup conditions and times, resulting in failure to meet operational requirements, influencing the normal function of the tunnel, and causing harm to the foundation structure, personnel, and property in severe cases. This article formulates a finite element numerical computation model for solid elements using three-dimensional elastic body theory and integrates field measurements to substantiate and ascertain the crucial parameter configurations of the finite element model. By proposing a comprehensive startup timing function for high-frequency dynamic machines under different startup conditions, simulating the frequency andmagnitude variations during the startup process, and suggesting functions for changes in frequency and magnitude, a simulated startup schedule function for high-frequency machines is created through coupling. Taking into account the selection of the transient dynamic analysis step length, the dynamic response results for the lower dynamic foundation during its fundamental frequency crossing process are obtained. The validation checks if the structural magnitude surpasses the safety threshold during the critical phase of unit startup traversing the structural resonance region. The design recommendations for high-frequency units' dynamic foundations are provided, taking into account the startup process of the machine and ensuring the safe operation of the tunnel. [ABSTRACT FROM AUTHOR]

Many Chinese have chosen to invest in Southeast Asian real estate in recent years. The term ‘rigid demander’ is used to refer to a subset of these enormous overseas real estate investment organizations. These three types of individuals consist of Chinese students, homosexuals, and retirees. This research uses the Analytical Hierarchy Process (AHP) to compare the political, economic, policy, market, and social environment of China’s real estate investments in Thailand and Malaysia from the perspectives of the aforementioned three types of individuals. This research’s data selection is based on the pre-COVID-19 normal situation (2018-2019). The research findings indicate that 1) Malaysia’s real estate investment environment is marginally superior to Thailand, but 2) Thailand’s market and social environments are more advantageous than Malaysia’s. For the three types mentioned in this research, the market and social environment have a more alluring effect. Therefore, the Thai government can increase its efforts in terms of the market, social, and policy environment to attract and serve Chinese investors, including these three types of Chinese, and to promote the growth and prosperity of the Thai real estate market.

Abstract Background Several biallelic truncating and missense variants of the gem nuclear organelle–associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early‐infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. Purpose This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub‐regional locations. Methods We performed whole‐exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype–phenotype relationship. Results Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147‐154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603‐154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression‐bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR‐like domain or RBS domain were more likely to be associated with epilepsy. Conclusions We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis.

Introduction Curing locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ) with surgery alone is challenging. Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients with locally advanced GC/GEJ, and SOX is the most common neoadjuvant regimen in China. The generally good tolerability in patients and fruquintinib’s low potential for drug–drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. A combination of fruquintinib, S-1 and oxaliplatin can be a promising neoadjuvant treatment for locally advanced GC/GEJ. In this phase II study, we aim to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC/GEJ.Methods and analysis The FRUTINEOGA trial is a prospective, multicentre, phase II, single-arm, open-label clinical trial that will enrol 54 patients. Eligible patients will be registered, enrolled and receive 2–4 cycles of fruquintinib plus SOX, after which surgery will be performed and tumour regression will be evaluated. The primary endpoint is the pathological remission rate, and the secondary endpoints are disease-free survival, overall survival, objective response rate, major pathological response rate and R0 resection rate.Ethics and dissemination Written informed consent will be required from all patients enrolled, and it will be provided by them. The study protocol received approval from the independent ethical review committee of Guangxi Medical University Cancer Hospital, Wuming Hospital of Guangxi Medical University and Wuzhou Red Cross Hospital, Wuzhou Gongren Hospital (approval number: CS2021(96)). We will submit the finalised paper for publication on completing the analyses. This study will provide valuable insights to clinicians regarding the safety and efficacy of incorporating fruquintinib into SOX as neoadjuvant treatment for locally advanced GC/GEJ. The findings have the potential to inform future research proposals and may guide the use of fruquintinib in the neoadjuvant setting for locally advanced GC/GEJ.Trial registration number NCT05122091.

ABSTRACT Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-β/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

NUS1 is responsible for encoding of the Nogo-B receptor (NgBR), which is a subunit of cis-prenyltransferase. Over 25 variants in NUS1 have been reported, and these variants have been found to be associated with various phenotypes, such as congenital disorders of glycosylation (CDG) and developmental and epileptic encephalopathy (DEE). We report on the case of a patient who presented with language and motor retardation, epilepsy, and electroencephalogram abnormalities. Upon conducting whole-exome sequencing, we discovered a novel pathogenic variant (chr6:118024873, NM_138459.5: c.791 + 6T>G) in NUS1, which was shown to cause Exon 4 to be skipped, resulting in a loss of 56 amino acids. Our findings strongly suggest that this novel variant of NUS1 is responsible for the development of neurological disorders, including epilepsy. It is believed that the truncation of Nogo-B receptor results in the loss of cis-prenyltransferase activity, which may be the underlying cause of the disease.

STXBP1 variants are one of the most common genetic causes of neurodevelopmental disorders and epilepsy, wherein STXBP1-related disorders are characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of affected patients. However, the spectrums of both genotype and phenotype are quite wide and diverse, with a high baseline variability even for recurrent STXBP1 variants. Until now, no clear genotype–phenotype correlations have been established and multiple disease mechanisms have been proposed for STXBP1-related disorders. Without an ascertained disease cause for many cases of STXBP1 variants, it is challenging to manage this disease in an effective manner and current symptom-based treatments are focused on seizure control only, which has a minimal impact on global development. A novel STXBP1 canonical splice variant, NM_001032221.4:c.578+2T>C, was reported in this study, together with detailed documentation of disease manifestations and treatment management. Further RNA expression analysis revealed abnormal intron retention and possible production of truncated STXBP1 proteins as a likely pathogenic mechanism. More importantly, the landscape of previously understudied STXBP1 splice variants and functional investigations was assessed for the first time to provide a context for the discussion of the complicated genotype–phenotype relationship of STXBP1-related disorders. Future cases of this disorder and a deeper mechanism-based understanding of its pathogenic cause are required for precision medicine and better disease management.

X-linked juvenile retinoschisis (XLRS), caused by the mutation of RS1 gene, is one of the most common causes of macular degeneration for male adolescents. The mutations and clinical manifestations of the disease are diverse. Neither the relationship between the genotypes and phenotypes, nor the radical treatment like gene therapy has been found by now. Retrospective studies have shown that carbonic anhydrase inhibitors can help reduce cysts. However, the specifically pharmacological mechanism remains unknown. Here, we culture induced pluripotent stem cells by drawing peripheral blood from a patient with XLRS, which are supposed to facilitate related researches.

Photon-counting LiDAR encounters interference from background noise in remote target detection, and the statistical detection of the accumulation of multiple pulses is necessary to eliminate the uncertainty of responses from the Geiger-mode avalanche photodiode (Gm-APD). The cumulative number of statistical detections is difficult to select due to the lack of effective evaluation of the influence of the background noise. In this work, a statistical detection signal evaluation method based on photon statistical entropy (PSE) is proposed by developing the detection process of the Gm-APD as an information transmission model. A prediction model for estimating the number of cumulative pulses required for high-accuracy ranging with the background noise is then established. The simulation analysis shows that the proposed PSE is more sensitive to the noise compared with the signal-to-noise ratio evaluation, and a minimum PSE exists to ensure all the range detections with background noise are close to the true range with a low and stable range error. The experiments demonstrate that the prediction model provides a reliable estimation of the number of required cumulative pulses in various noise conditions. With the estimated number of cumulative pulses, when the signal photons are less than 0.1 per pulse, the range accuracy of 4.1 cm and 5.3 cm are obtained under the background noise of 7.6 MHz and 5.1 MHz, respectively.

X-linked juvenile retinoschisis (XLRS) is an inherited disease characterized by splitting within inner retinal layers and impaired vision, which begins in childhood and occurs mostly in males. Peripheral blood mononuclear cells (PBMCs) were isolated from a seven-year-old boy carrying a hemizygous mutation in RS1 gene, and were reprogrammed into human induced pluripotent stem cells (iPSCs) using non-integrative episomal vectors. The cell line, ZOCi003-A, had normal karyotype, expressed pluripotency markers, and could differentiate into three germ layers in vivo. This IPSC line may be used for studying the molecular basis of XLRS and selecting potential therapeutic targets and drugs.

ARR3 has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES), we identified the first high myopia case with hemizygous ARR3-related mutation in a male patient in a Southern Chinese family. This novel truncated mutation (ARR3: c.569C>G, p.S190*) co-segregated with the disease phenotype in affected family members and demonstrated that high myopia caused by ARR3 is not X-linked, female-limited, where a complicated X-linked inheritance pattern may exist. Thus, our case expanded the variant spectrum in ARR3 and provided additional information for genetic counseling, prenatal testing, and diagnosis. Moreover, we characterized the nonsense-mediated decay of the ARR3 mutant mRNA and discussed the possible underlying pathogenic mechanisms.

ABSTRACT There is a critical need for new antifungal drugs; however, the lack of available fungus-specific targets is a major hurdle in the development of antifungal therapeutics. Spore germination is a differentiation process absent in humans that could harbor uncharacterized fungus-specific targets. To capitalize on this possibility, we developed novel phenotypic assays to identify and characterize inhibitors of spore germination of the human fungal pathogen Cryptococcus. Using these assays, we carried out a high-throughput screen of ∼75,000 drug-like small molecules and identified and characterized 191 novel inhibitors of spore germination, many of which also inhibited yeast replication and demonstrated low cytotoxicity against mammalian cells. Using an automated, microscopy-based, quantitative germination assay (QGA), we discovered that germinating spore populations can exhibit unique phenotypes in response to chemical inhibitors. Through the characterization of these spore population dynamics in the presence of the newly identified inhibitors, we classified 6 distinct phenotypes based on differences in germination synchronicity, germination rates, and overall population behavior. Similar chemical phenotypes were induced by inhibitors that targeted the same cellular function or had shared substructures. Leveraging these features, we used QGAs to identify outliers among compounds that fell into similar structural groups and thus refined relevant structural moieties, facilitating target identification. This approach led to the identification of complex II of the electron transport chain as the putative target of a promising structural cluster of germination inhibitory compounds. These inhibitors showed high potency against Cryptococcus spore germination while maintaining low cytotoxicity against mammalian cells, making them prime candidates for development into novel antifungal therapeutics. IMPORTANCE Fungal pathogens cause 1.5 million deaths annually, and there is a critical need for new antifungal drugs. However, humans and fungi are very similar on a molecular level, and so many drugs that kill fungi also damage human cells, leading to extreme side effects, including death. The lack of fungus-specific targets is a major hurdle in the development of antifungal therapeutics. Spore germination is a process absent in humans that could harbor fungus-specific targets. To capitalize on this possibility, we developed new assays to identify and characterize inhibitors of spore germination of the human fungal pathogen Cryptococcus. Using these assays, we identified and characterized 191 novel inhibitors of spore germination. These inhibitors showed high potency against Cryptococcus spore germination while maintaining low cytotoxicity against mammalian cells, making them prime candidates for development into novel antifungal therapeutics.

Susceptibility to idiopathic generalized epilepsy-15 (EIG15) is an autosomal dominant seizure disorder characterized by onset of variable types of seizures in the first decade, caused by heterozygous mutations in the RORB gene encoding the retinoid-related orphan receptor β. We established an induced pluripotent stem cell (iPSC) line from PBMCs collected from a five-year-old female patient with EIG15, via reprogramming with OCT3/4, SOX2, KLF4, and c-MYC. Upon careful examination, the iPSCs stably expressed pluripotent genes, maintained a normal karyotype, and had full potential for three-germ layer differentiation.

Abstract The bacterial microbiota in the gut varies among species, as well as with habitat, diet, age, and other factors. Intestinal microbiota homeostasis allows a host to adjust metabolic and immune performances in response to environmental changes. Therefore, potential implications of the gut microbiota in sustaining the health of the host have gained increasing attention in the field of endangered animal conservation. However, the effect of host intraspecies genetic variation on the gut microbiota is unknown. Moreover, little is known about the complexity of the gut mycobiota. Tigers are listed as endangered species, raising worldwide concern. Potential influences of subspecies, diet, and age on the gut microbiota in tigers were investigated in this study to provide a better understanding of the response of the tiger gut microbiota to external changes. The results revealed that the impacts of the factors listed above on gut bacterial and fungal communities are versatile. Host intraspecies genetic variation significantly impacted only fungal alpha diversity of the gut microbiota. Differences in diet, on the other hand, had a significant impact on alpha diversity of the gut microbiota, but exerted different effects on beta diversity of gut bacterial and fungal communities. Host age had no significant impact on the diversity of the gut fungal communities, but significantly impacted beta diversity of gut bacterial communities. This comprehensive study of tiger gut microbiota is an essential reference for tiger conservation when considering feeding and management strategies, and will contribute to a better understanding of the mycobiota in wildlife.

Spores are essential for the long-term survival of many diverse organisms, due to their roles in reproduction and stress resistance. In the environmental human fungal pathogen, Cryptococcus, basidiospores are robust cells with the ability to cause disease in animal models of infection. Here we describe methods for producing and purifying Cryptococcus basidiospores in quantities sufficient for large-scale analyses. The production of high numbers of pure spores has facilitated the development of new assays, including quantitative germination assays, and enabled transcriptomic, proteomic, and virulence studies, leading to discoveries of behaviors and properties unique to spores and spore-mediated disease.

Photon counting lidar for long-range detection faces the problem of declining ranging performance caused by background noise. Current anti-noise methods are not robust enough in the case of weak signal and strong background noise, resulting in poor ranging error. In this work, based on the characteristics of the uncertainty of echo signal and noise in photon counting lidar, an entropy-based anti-noise method is proposed to reduce the ranging error under high background noise. Firstly, the photon counting entropy, which is considered as the feature to distinguish signal from noise, is defined to quantify the uncertainty of fluctuation among photon events responding to the Geiger mode avalanche photodiode. Then, the photon counting entropy is combined with a windowing operation to enhance the difference between signal and noise, so as to mitigate the effect of background noise and estimate the time of flight of the laser pulses. Simulation and experimental analysis show that the proposed method improves the anti-noise performance well, and experimental results demonstrate that the proposed method effectively mitigates the effect of background noise to reduce ranging error despite high background noise.

Background. The present work aims at formulating the melatonin-loaded nanoparticles (MTNPs) exhibiting the controlled-release and pH-sensitivity to repurpose the use of melatonin in the treatment of depressive-like behaviors and hypothalamus-pituitary-adrenal (HPA) axis dysregulation. Methods. MTNPs were characterized for the size, drug incorporation, and in vitro release in the different pH environments. Its merits were in vivo tested on the pinealectomized rats presenting the depressive-like behaviors and the abnormal HPA axis activity by calculating the improvement on saccharin preference, swimming immobility time, and the negative feedback of HPA axis. Results. Results revealed that MTNPs showed nanometer size, 15.77% of drug loading, 33.82% of encapsulation efficiency, the different controlled-release profiles in different pH environments (pH 1.2, pH 6.8, and pH 7.4), more sensitivity release in simulated intestinal fluid (pH 7.4) and blood (pH 6.8), and less sensitivity release in simulated gastric fluid (pH 1.2). Furthermore, MTNPs displayed better antidepressant actions in reducing the immobility time of forced swimming test, increasing the preference for saccharin, and sensitizing the blunt negative feedback of HPA axis, when compared to the free melatonin. Conclusions. The controlled-release nanoparticles is shown to be an effective improvement on the dosage form for melatonin, which is worthy of futuristic and complete evaluation.

Spores are an essential cell type required for long-term survival across diverse organisms in the tree of life and are a hallmark of fungal reproduction, persistence, and dispersal. Among human fungal pathogens, spores are presumed infectious particles, but relatively little is known about this robust cell type. Here we used the meningitis-causing fungus Cryptococcus neoformans to determine the roles of spore-resident proteins in spore biology. Using highly sensitive nanoscale liquid chromatography/mass spectrometry, we compared the proteomes of spores and vegetative cells (yeast) and identified eighteen proteins specifically enriched in spores. The genes encoding these proteins were deleted, and the resulting strains were evaluated for discernable phenotypes. We hypothesized that spore-enriched proteins would be preferentially involved in spore-specific processes such as dormancy, stress resistance, and germination. Surprisingly, however, the majority of the mutants harbored defects in sexual development, the process by which spores are formed. One mutant in the cohort was defective in the spore-specific process of germination, showing a delay specifically in the initiation of vegetative growth. Thus, by using this in-depth proteomics approach as a screening tool for cell type-specific proteins and combining it with molecular genetics, we successfully identified the first germination factor in C. neoformans. We also identified numerous proteins with previously unknown functions in both sexual development and spore composition. Our findings provide the first insights into the basic protein components of infectious spores and reveal unexpected molecular connections between infectious particle production and spore composition in a pathogenic eukaryote.