Advances in TRPV6 inhibitors for tumors by targeted therapies: Macromolecular proteins, synthetic small molecule compounds, and natural compounds.

TRPV6, a Ca2+-selective member of the transient receptor potential vanilloid (TRPV) family, plays a key role in extracellular calcium transport, calcium ion reuptake, and maintenance of a local low calcium environment. An increasing number of studies have shown that TRPV6 is involved in the regulation of various diseases. Notably, overexpression of TRPV6 is closely related to the occurrence of various cancers. Research confirmed that knocking down TRPV6 could effectively reduce the proliferation and invasiveness of tumors by mainly mediating the calcium signaling pathway. Hence, TRPV6 has become a promising new drug target for numerous tumor treatments. However, the development of TRPV6 inhibitors is still in the early stage, and the existing TRPV6 inhibitors have poor selectivity and off-target effects. In this review, we focus on summarizing and describing the structure characters, and mechanisms of existing TRPV6 inhibitors to provide new ideas and directions for the development of novel TRPV6 inhibitors.

TREATMENT OF COMATOSE SURVIVORS OF IN-HOSPITAL CARDIAC ARREST WITH EXTENDED ENDOVASCULAR COOLING METHOD FOR 72 H: A PROPENSITY SCORE-MATCHED ANALYSIS.

ABSTRACT: Aims: Targeted temperature management is recommended for at least 24 h in comatose survivors of in-hospital cardiac arrest (IHCA) after the return of spontaneous circulation; however, whether an extension for 72 h leads to better neurological outcomes is uncertain. Methods: We included data from the Qilu Hospital of Shandong University between July 20, 2019, and June 30, 2022. Unconscious patients who had return of spontaneous circulation lasting >20 consecutive min and received endovascular cooling (72 h) or normothermia treatment were compared in terms of survival-to-discharge and favorable neurological survival. Propensity score matching was used to formulate balanced 1:3 matched patients. Results: In total, 2,084 patients were included. Sixteen patients received extended endovascular cooling and 48 matched controls received normothermia therapy. Compared with the normothermia group, patients who received prolonged endovascular cooling had a higher survival-to-discharge rate. However, good neurological outcomes did not differ significantly. Before matching, Cox regression analysis, using mortality as the event, showed that extended endovascular cooling independently affected the survival of IHCA patients. Conclusions: Among comatose patients who had been resuscitated from IHCA, the use of endovascular cooling for 72 h might confer a benefit on survival-to-discharge.

TDCAU-Net: retinal vessel segmentation using transformer dilated convolutional attention-based U-Net method.

Retinal vessel segmentation plays a vital role in the medical field, facilitating the identification of numerous chronic conditions based on retinal vessel images. These conditions include diabetic retinopathy, hypertensive retinopathy, glaucoma, and others. Although the U-Net model has shown promising results in retinal vessel segmentation, it tends to struggle with fine branching and dense vessel segmentation. To further enhance the precision of retinal vessel segmentation, we propose a novel approach called transformer dilated convolution attention U-Net (TDCAU-Net), which builds upon the U-Net architecture with improved Transformer-based dilated convolution attention mechanisms. The proposed model retains the three-layer architecture of the U-Net network. The Transformer component enables the learning of contextual information for each pixel in the image, while the dilated convolution attention prevents information loss. The algorithm efficiently addresses several challenges to optimize blood vessel detection. The process starts with five-step preprocessing of the images, followed by chunking them into segments. Subsequently, the retinal images are fed into the modified U-Net network introduced in this paper for segmentation. The study employs eye fundus images from the DRIVE and CHASEDB1 databases for both training and testing purposes. Evaluation metrics are utilized to compare the algorithm's results with state-of-the-art methods. The experimental analysis on both databases demonstrates that the algorithm achieves high values of sensitivity, specificity, accuracy, and AUC. Specifically, for the first database, the achieved values are 0.8187, 0.9756, 0.9556, and 0.9795, respectively. For the second database, the corresponding values are 0.8243, 0.9836, 0.9738, and 0.9878, respectively. These results demonstrate that the proposed approach outperforms state-of-the-art methods, achieving higher performance on both datasets. The TDCAU-Net model presented in this study exhibits substantial capabilities in accurately segmenting fine branching and dense vessels. The segmentation performance of the network surpasses that of the U-Net algorithm and several mainstream methods.

Manipulation of Spin-Orbit Torque in Tungsten Oxide/Manganite Heterostructure by Ionic Liquid Gating and Orbit Engineering.

Spin-orbit coupling (SOC) is the interaction between electron's spin and orbital motion, which could realize a charge-to-spin current conversion and enable an innovative method to switch the magnetization by spin-orbit torque (SOT). Varied techniques have been developed to manipulate and improve the SOT, but the role of the orbit degree of freedom, which should have a crucial bearing on the SOC and SOT, is still confusing. Here, we find that the charge-to-spin current conversion and SOT in W3O8-δ/(La, Sr)MnO3 could be produced or eliminated by ionic liquid gating. Through tuning the preferential occupancy of Mn/W-d electrons from the in-plane (dx2-y2) to out-of-plane (d3z2-r2) orbit, the SOT damping-like field efficiency is nearly doubled due to the enhanced spin Hall effect and interfacial Rashba-Edelstein effect. These findings not only offer intriguing opportunities to control the SOT for high-efficient spintronic devices but also could be a fundamental step toward spin-orbitronics in the future.

Demodulation of the overlapping reflection spectrum of serial FBGs based on a weighted differential evolution algorithm.

This study addresses the wavelength demodulation problem of the overlapping reflection spectrum of serial fiber Bragg gratings (FBGs) with nearly-identical wavelength. Specifically, a novel demodulation model for the overlapping reflection spectrum was presented based on spectrum similarity, and this model encodes FBGs through reflectivity. Subsequently, a weighted differential evolution algorithm was employed to calculate the FBG wavelengths. And the factors affecting the demodulation accuracy of the proposed method were simulated and analyzed. Finally, the proposed method was applied to demodulate the overlapping reflection spectra of serial FBGs. The experiment results indicate that the proposed method is suitable for completely overlapping, partially overlapping, and non-overlapping reflection spectra of serial FBGs. The wavelength demodulation accuracy demonstrated here in fully overlapping situations for two, three, and four FBGs was only 4.5, 14.9, and 24.6 pm, respectively.

Analysis of the effect of PCR testing and antigen testing on controlling the transmission for Omicron based on different scenarios.

After the policy adjustment, China no longer carries out COVID-19 PCR testing for all people, and antigen testing has become the main way to detect and manage infectious sources. We developed a dynamic model to evaluate and compare the effects between PCR and antigen testing for controlling the pandemic. Due to the increase of contact degree, the peak reduction effect of PCR testing in population is lower than that of antigen testing. Even if it was only 20% of people isolated at home after antigen testing, the peak of the epidemic could be reduced by 9.46%. If the proportion of antigen testing is further increased to 80%, the peak of the pandemic can be reduced by 31.41%. Antigen testing performed better effects in school (reduction proportion 29.27%) and community (29.34%) than in workplace (27.75%). Therefore, we recommend that antigen testing in the population should be encouraged during the pandemic, and home isolation of infected persons should be advocated, especially in crowded places. To improve the availability of antigen, the testing proportion should be further enhanced.

MCSF-Net: a multi-scale channel spatial fusion network for real-time polyp segmentation.

Colorectal cancer is a globally prevalent cancer type that necessitates prompt screening. Colonoscopy is the established diagnostic technique for identifying colorectal polyps. However, missed polyp rates remain a concern. Early detection of polyps, while still precancerous, is vital for minimizing cancer-related mortality and economic impact. In the clinical setting, precise segmentation of polyps from colonoscopy images can provide valuable diagnostic and surgical information. Recent advances in computer-aided diagnostic systems, specifically those based on deep learning techniques, have shown promise in improving the detection rates of missed polyps, and thereby assisting gastroenterologists in improving polyp identification. In the present investigation, we introduce MCSF-Net, a real-time automatic segmentation framework that utilizes a multi-scale channel space fusion network. The proposed architecture leverages a multi-scale fusion module in conjunction with spatial and channel attention mechanisms to effectively amalgamate high-dimensional multi-scale features. Additionally, a feature complementation module is employed to extract boundary cues from low-dimensional features, facilitating enhanced representation of low-level features while keeping computational complexity to a minimum. Furthermore, we incorporate shape blocks to facilitate better model supervision for precise identification of boundary features of polyps. Our extensive evaluation of the proposed MCSF-Net on five publicly available benchmark datasets reveals that it outperforms several existing state-of-the-art approaches with respect to different evaluation metrics. The proposed approach runs at an impressive ∼45 FPS, demonstrating notable advantages in terms of scalability and real-time segmentation.

ECTransNet: An Automatic Polyp Segmentation Network Based on Multi-scale Edge Complementary.

Colonoscopy is acknowledged as the foremost technique for detecting polyps and facilitating early screening and prevention of colorectal cancer. In clinical settings, the segmentation of polyps from colonoscopy images holds paramount importance as it furnishes critical diagnostic and surgical information. Nevertheless, the precise segmentation of colon polyp images is still a challenging task owing to the varied sizes and morphological features of colon polyps and the indistinct boundary between polyps and mucosa. In this study, we present a novel network architecture named ECTransNet to address the challenges in polyp segmentation. Specifically, we propose an edge complementary module that effectively fuses the differences between features with multiple resolutions. This enables the network to exchange features across different levels and results in a substantial improvement in the edge fineness of the polyp segmentation. Additionally, we utilize a feature aggregation decoder that leverages residual blocks to adaptively fuse high-order to low-order features. This strategy restores local edges in low-order features while preserving the spatial information of targets in high-order features, ultimately enhancing the segmentation accuracy. According to extensive experiments conducted on ECTransNet, the results demonstrate that this method outperforms most state-of-the-art approaches on five publicly available datasets. Specifically, our method achieved mDice scores of 0.901 and 0.923 on the Kvasir-SEG and CVC-ClinicDB datasets, respectively. On the Endoscene, CVC-ColonDB, and ETIS datasets, we obtained mDice scores of 0.907, 0.766, and 0.728, respectively.

Electrical Control of Spin Hall Efficiency and Field-Free Magnetization Switching in W/Pt/Co/Pt Heterostructures with Competing Spin Currents.

Reversal of magnetization via current-induced spin-orbit torque (SOT) is one of the core issues in spintronics. However, an in-plane assistant field is usually required for the deterministic switching of a perpendicularly magnetized system. Additionally, the efficiency of SOT is low, which is detrimental to device applications. This study achieved a reversible and non-volatile control of the critical current for magnetization switching and spin Hall efficiency in the TaN/W/Pt/Co/Pt/TaN heterostructures by ionic liquid (IL) gating-induced hydrogen ion adsorption and desorption in the upper Pt layer. Furthermore, the thinning of the Pt and TaN capping layers activated the oxygen ion migration toward the Co layer under IL gating, resulting in an exchange bias field and allowing field-free magnetization switching and Boolean logic operation. The results of this study offer an intriguing opportunity to promote the development of SOT-based spintronic devices from the perspective of iontronics with low energy dissipation.

Review: Acetylation mechanisms and targeted therapies in cardiac fibrosis.

Cardiac fibrosis is a common pathophysiological remodeling process that occurs in a variety of cardiovascular diseases and greatly influences heart structure and function, progressively leading to the development of heart failure. However, to date, few effective therapies for cardiac fibrosis exist. Abnormal proliferation, differentiation, and migration of cardiac fibroblasts are responsible for the excessive deposition of extracellular matrix in the myocardium. Acetylation, a widespread and reversible protein post-translational modification, plays an important role in the development of cardiac fibrosis by adding acetyl groups to lysine residues. Many acetyltransferases and deacetylases regulate the dynamic alterations of acetylation in cardiac fibrosis, regulating a range of pathogenic conditions including oxidative stress, mitochondrial dysfunction, and energy metabolism disturbance. In this review, we demonstrate the critical roles that acetylation modifications caused by different types of pathological injury play in cardiac fibrosis. Furthermore, we propose therapeutic acetylation-targeting strategies for the prevention and treatment of patients with cardiac fibrosis.

The benefits of neoadjuvant therapy for patients with resectable pancreatic cancer: an updated systematic review and meta-analysis.

Neoadjuvant therapy (NAT) was effective in improving overall survival (OS) of borderline resectable pancreatic cancer. However, its application in resectable pancreatic cancer remains controversial. This study aimed to determine whether NAT has a greater advantage over conventional upfront surgery (US) in terms of resection rate, R0 resection rate, positive lymph node rate, and OS. We identified articles before October 7, 2022, by searching four electronic databases. The studies included in the meta-analysis all met the inclusion and exclusion criteria. The Newcastle-Ottawa scale was used to evaluate the quality of the articles. OS, DFS, resection rate, R0 resection rate and positive lymph nodes rate were extracted. Odds ratio (OR), hazard ratio (HR) and 95% confidence intervals (CI) were calculated, and sensitivity analysis and publication bias were used to assess the sources of heterogeneity. In total, 24 studies, involving 1384 (35.66%) patients assigned to NAT and 2497 (64.43%) patients assigned to US, were included in the analysis. NAT could effectively prolong OS (HR 0.73, 95% CI 0.65-0.82, P < 0.001) and DFS (HR 0.72, 95% CI 0.62-0.84, P < 0.001). Subgroup analysis results of 6 randomized controlled trials (RCTs) also showed that RPC patients could benefit from NAT in the long term (HR 0.72, 95% CI 0.58-0.90, P = 0.003). NAT decreased resection rate (OR 0.43, 95% CI 0.33-0.55, P < 0.001), but was associated with increased R0 resection rate (OR 2.05, 95% CI 1.47-2.88, P < 0.001) and decreased positive lymph node rate (OR 0.38, 95% CI 0.27-0.52, P < 0.001). Although the application of NAT increases the risk of patients not being able to undergo surgical resection, it can prolong the OS and delay tumor progression in RPC. Therefore, we still expect larger and higher-quality RCTs to confirm the effectiveness of NAT.

ABI5 promotes heat stress-induced chlorophyll degradation by modulating the stability of MYB44 in cucumber.

The yellowing of leaves caused by the decomposition of chlorophyll (Chl) is a characteristic event during senescence, which can be induced by various environmental stresses. However, the molecular mechanisms of high temperature-induced Chl degradation in horticultural plants remain poorly understood. Here, we found that heat stress induced Chl degradation and the expression of ABI5 and MYB44 in cucumber. Silencing of ABI5 compromised heat stress-induced Chl degradation, and the transcription of pheophytinase (PPH) and pheophorbide a oxygenase (PAO), two key genes in Chl catabolic pathway, but silencing of MYB44 exhibited the opposite results. Furthermore, ABI5 interacted with MYB44 in vitro and in vivo. ABI5 positively regulated heat stress-induced Chl degradation through two pathways. ABI5 directly bound to PPH and PAO promoters to promote their expression, leading to accelerating Chl degradation. On the other hand, the interaction between ABI5 and MYB44 reduced the binding of MYB44 to PPH and PAO promoters and led to the ubiquitination-depended protein degradation of MYB44, thereby alleviating the transcription inhibitory effect of MYB44 on PPH and PAO. Taken together, our findings propose a new regulatory network for ABI5 in regulating heat stress-induced Chl degradation.

Control of Compensation Temperature in CoGd Films through Hydrogen and Oxygen Migration under Gate Voltage.

Electrical control of magnetic properties is crucial for low-energy memory and logic spintronic devices. We find that the magnetic properties of ferrimagnetic CoGd can be altered through ionic liquid gating. Gate voltages manipulate the opposite magnetic moments in Co and Gd sublattices and induce a giant magnetic compensation temperature change of more than 200 K in Pt/CoGd/Pt heterostructures. The electrically controlled dominant magnetic sublattice allows voltage-induced magnetization switching. Both experiments and theoretical calculations demonstrate that the significant modulations of compensation temperature are relevant to the reduced Gd moments due to the presence of hydrogen ions at positive voltages as well as the enhanced Co moments and reduced Gd moments due to the injection of oxygen ions at negative voltages. These findings expand the possibilities for all-electric and reversible magnetization control in the field of spintronics.

Model-based risk assessment of dengue fever transmission in Xiamen City, China.

Background: Quantitative assessment of the risk of local transmission from imported dengue cases makes a great challenge to the development of public health in China. The purpose of this study is to observe the risk of mosquito-borne transmission in Xiamen City through ecological and insecticide resistance monitoring. Quantitative evaluation of mosquito insecticide resistance, community population and the number of imported cases affecting the transmission of dengue fever (DF) in Xiamen was carried out based on transmission dynamics model, so as to reveal the correlation between key risk factors and DF transmission. Methods: Based on the dynamics model and combined with the epidemiological characteristics of DF in Xiamen City, a transmission dynamics model was built to simulate the secondary cases caused by imported cases to evaluate the transmission risk of DF, and to explore the influence of mosquito insecticide resistance, community population and imported cases on the epidemic situation of DF in Xiamen City. Results: For the transmission model of DF, when the community population is between 10,000 and 25,000, changing the number of imported DF cases and the mortality rate of mosquitoes will have an impact on the spread of indigenous DF cases, however, changing the birth rate of mosquitoes did not gain more effect on the spread of local DF transmission. Conclusions: Through the quantitative evaluation of the model, this study determined that the mosquito resistance index has an important influence on the local transmission of dengue fever caused by imported cases in Xiamen, and the Brayton index can also affect the local transmission of the disease.

Switchable Giant Bulk Photocurrents and Photo-spin-currents in Monolayer PT-Symmetric Antiferromagnet MnPSe3.

Converting light into steady currents and spin-currents in two-dimensional (2D) platform is essential for future energy harvesting and spintronics. We show that the giant and modulable bulk photovoltaic effects (BPVEs) can be achieved in air-stable 2D antiferromagnet (AFM) monolayer MnPSe3, with nonlinear photoconductance >4000 nm·µA/V2 and photo-spin-conductance >2000 (nm·µA/V2ℏ/2e) in the visible spectrum. The propagation and the spin-polarizations of photocurrents can be switched via simply rotating the Néel vector. We unveil that the PT-symmetry, mirror symmetries, and spin-orbital-couplings are the keys for the observed sizable and controllable 2D BPVEs. All the results provide insights into the BPVEs of 2D AFM and suggest that the layered MnPSe3 is an outstanding 2D platform for energy device and photo-spintronics.

Enhanced Spin Current in Ni81 Fe19 /Cu-CuOx Bilayer with Top and Sideways Oxidization.

Generation and manipulation of spin current are the cores of spintronic devices, which are intensely pursued. Heavy metals with strong spin-orbit coupling are commonly used for the generation of spin current, but are incompatible with the mass production of devices, and the polarization of spin current is limited to be in-plane. Here, it is shown that the spin current with strong out-of-plane polarization component can be generated and transmitted in Ni81 Fe19 /Cu-CuOx bilayer with sideways and top oxidizations. The charge-to-spin current conversion efficiency can be enhanced through the spin currents consisting of both out-of-plane polarization (σz ) and in-plane polarization (σy ) induced by spin-vorticity coupling. Such a spin current is demonstrated to be closely related to the lateral oxidization gradient and can be controlled by changing the temperatures and times of annealing. The finding here provides a novel degree of freedom to produce and control the spin current in spintronic devices.

A Survey on Differential Privacy for Medical Data Analysis.

Machine learning methods promote the sustainable development of wise information technology of medicine (WITMED), and a variety of medical data brings high value and convenience to medical analysis. However, the applications of medical data have also been confronted with the risk of privacy leakage that is hard to avoid, especially when conducting correlation analysis or data sharing among multiple institutions. Data security and privacy preservation have recently played an essential role in the field of secure and private medical data analysis, where many differential privacy strategies are applied to medical data publishing and mining. In this paper, we survey research work on the applications of differential privacy for medical data analysis, discussing the necessity of medical privacy-preserving, the advantages of differential privacy, and their applications to typical medical data, such as genomic data and wearable device data. Furthermore, we discuss the challenges and potential future research directions for differential privacy in medical applications.

Age-specific transmission dynamic of mumps: A long-term large-scale modeling study in Jilin Province, China.

Objectives: Despite the adoption of a new childhood immunization program in China, the incidence of mumps remains high. This study aimed to describe the epidemiological characteristics of mumps in Jilin Province from 2005 to 2019 and to assess the transmissibility of mumps virus among the whole population and different subgroups by regions and age groups. Methods: The Non-age-specific and age-specific Susceptible-Exposed-Pre-symptomatic-Infectious-Asymptomatic-Recovered (SEPIAR) models were fitted to actual mumps incidence data. The time-varying reproduction number (R t ) was used to evaluate and compare the transmissibility. Results: From 2005 to 2019, a total of 57,424 cases of mumps were reported in Jilin Province. The incidence of mumps was the highest in people aged 5 to 9 years (77.37 per 100,000). The two SEPIAR models fitted the reported data well (P < 0.01). The median transmissibility (R t ) calculated by the two SEPIAR models were 1.096 (range: 1.911 × 10-5-2.192) and 1.074 (range: 0.033-2.114) respectively. The age-specific SEPIAR model was more representative of the actual epidemic of mumps in Jilin Province from 2005-2019. Conclusions: For mumps control, it is recommended that mumps-containing vaccines (MuCV) coverage be increased nationwide in the 5-9 years age group, either by a mumps vaccine alone or by a combination of vaccines such as measles-mumps-rubella (MMR) vaccine. The coverage of vaccines in Jilin Province should be continuously expanded to establish solid immunity in the population. China needs to redefine the optimal time interval for MuCV immunization.

Application of logistic differential equation models for early warning of infectious diseases in Jilin Province.

BACKGROUND: There is still a relatively serious disease burden of infectious diseases and the warning time for different infectious diseases before implementation of interventions is important. The logistic differential equation models can be used for predicting early warning of infectious diseases. The aim of this study is to compare the disease fitting effects of the logistic differential equation (LDE) model and the generalized logistic differential equation (GLDE) model for the first time using data on multiple infectious diseases in Jilin Province and to calculate the early warning signals for different types of infectious diseases using these two models in Jilin Province to solve the disease early warning schedule for Jilin Province throughout the year. METHODS: Collecting the incidence of 22 infectious diseases in Jilin Province, China. The LDE and GLDE models were used to calculate the recommended warning week (RWW), the epidemic acceleration week (EAW) and warning removed week (WRW) for acute infectious diseases with seasonality, respectively. RESULTS: Five diseases were selected for analysis based on screening principles: hemorrhagic fever with renal syndrome (HFRS), shigellosis, mumps, Hand, foot and mouth disease (HFMD), and scarlet fever. The GLDE model fitted the above diseases better (0.80 ≤ R2 ≤ 0.94, P <  0. 005) than the LDE model. The estimated warning durations (per year) of the LDE model for the above diseases were: weeks 12-23 and 40-50; weeks 20-36; weeks 15-24 and 43-52; weeks 26-34; and weeks 16-25 and 41-50. While the durations of early warning (per year) estimated by the GLDE model were: weeks 7-24 and 36-51; weeks 13-37; weeks 11-26 and 39-54; weeks 23-35; and weeks 12-26 and 40-50. CONCLUSIONS: Compared to the LDE model, the GLDE model provides a better fit to the actual disease incidence data. The RWW appeared to be earlier when estimated with the GLDE model than the LDE model. In addition, the WRW estimated with the GLDE model were more lagged and had a longer warning time.