Benzothiazole derivatives as histone deacetylase inhibitors for the treatment of autosomal dominant polycystic kidney disease.

Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). The selected compound significantly prevented cyst formation and expansion in an in vitro cyst model and was efficacious in reducing cyst growth in both an embryonic kidney cyst model and an in vivo ADPKD mouse model. Our results provided compelling evidence that compound 26 represents a new HDAC inhibitor for the treatment of ADPKD.

Immune responses to inactivated COVID-19 vaccine were decreased in Chinese patients with chronic respiratory diseases.

Purpose: The effectiveness of inactivated vaccines against acute respiratory syndrome coronavirus 2 (SARS­CoV­2), the causative agent of coronavirus disease 2019 (COVID-19), has become a global concern. Hence, the aim of this study was to evaluate vaccine safety and to assess immune responses in individuals with chronic respiratory disease (CRD) following a two-dose vaccination. Methods: The study cohort included 191 participants (112 adult CRD patients and 79 healthy controls [HCs]) at least 21 (range, 21-159) days after a second vaccination. Frequencies of memory B cells (MBCs) subsets and titers of SARS-CoV-2 neutralizing antibodies (NAbs) and anti-receptor binding domain (RBD) IgG antibodies (Abs) were analyzed. Results: As compared to the HCs, CRD patients had lower seropositivity rates and titers of both anti-RBD IgG Abs and NAbs, in addition to lower frequencies of RBD-specific MBCs (all, p < 0.05). At 3 months, CRD patients had lower seropositivity rates and titers of anti-RBD IgG Abs than the HCs (p < 0.05). For CoronaVac, the seropositivity rates of both Abs were lower in patients with old pulmonary tuberculosis than HCs. For BBIBP-CorV, the seropositivity rates of CoV-2 NAbs were lower in patients with chronic obstructive pulmonary disease than HCs (all, p < 0.05). Meanwhile, there was no significant difference in overall adverse events between the CRD patients and HCs. Univariate and multivariate analyses identified the time interval following a second vaccination as a risk factor for the production of anti-RBD IgG Abs and CoV-2 NAbs, while the CoronaVac had a positive effect on the titers of both Abs. Female was identified as a protective factor for CoV-2 NAb levels. Conclusion: Inactivated COVID-19 vaccines were safe and well tolerated by CRD patients but resulted in lower Ab responses and the frequencies of RBD-specific MBCs. Therefore, CRD patients should be prioritized for booster vaccinations.

Electrochemically Imaging the Response of Ion-Selective Membranes with an Ultralow Detection Limit.

The development of ion-selective membranes for the selective response of a particular ion has been studied for many years; however, imaging the response of the membrane with a low detection limit is challenging. Here, high spatial-resolution electrochemical imaging of this response down to picomolar is achieved using scanning ion conductive microscopy. The detection strategy relies on the exclusion of a small amount of counter ions from the membrane in the presence of a low concentration of target ions in the solution. These excluded counter ions are adsorbed at the membrane-solution interface, leading to more positive charges at the surface. The resultant elevation of the ionic current in the approach curve behaves as the response for the target ions down to 10-11 M, which is much more sensitive than that using potentiometric measurement. The constant-current scanning of the membrane exhibits the fluctuation of the apparent surface height that is correlated with the ionic concentration, permitting the imaging of the response at the nanoscale. The achievement of highly sensitive and spatial-resolution imaging for the ionic response enable the collection of spatial response at the ion-selective membrane, which will greatly advance the study of ion-selective electrodes.

Chordin-like 1 is a novel prognostic biomarker and correlative with immune cell infiltration in lung adenocarcinoma.

Chordin-like 1 (CHRDL1), an inhibitor of bone morphogenetic proteins(BMPs), has been recently reported to participate in the progression of numerous tumors, however, its role in lung adenocarcinoma (LUAD) remains unclear. Our study aimed to demonstrate relationship between CHRDL1 and LUAD based on data from The Cancer Genome Atlas (TCGA). Among them, CHRDL1 expression revealed promising power for distinguishing LUAD tissues form normal sample. Low CHRDL1 was correlated with poor clinicopathologic features, including high T stage (OR=0.45, P<0.001), high N stage (OR=0.57, P<0.003), bad treatment effect (OR=0.64, P=0.047), positive tumor status (OR=0.63, P=0.018), and TP53 mutation (OR=0.49, P<0.001). The survival curve illustrated that low CHRDL1 was significantly correlative with a poor overall survival (HR=0.60, P<0.001). At multivariate Cox regression analysis, CHRDL1 remained independently correlative with overall survival. GSEA identified that the CHRDL1 expression was related to cell cycle and immunoregulation. Immune infiltration analysis suggested that CHRDL1 was significantly correlative with 7 kinds of immune cells. Immunohistochemical validation showed that CHRDL1 was abnormally elevated and negatively correlated with Th2 cells in LUAD tissues. In conclusion, CHRDL1 might become a novel prognostic biomarker and therapy target in LUAD. Moreover, CHRDL1 may improve the effectiveness of immunotherapy by regulating immune infiltration.

Intrinsic magnetism and biaxial strain tuning in two-dimensional metal halides V3X8 (X = F, Cl, Br, I) from first principles and Monte Carlo simulation.

A novel family of two-dimensional (2D) crystalline metal superhalogens V3X8 (X = F, Cl, Br, I) with intrinsic magnetism was predicted using first-principles calculations in the framework of density functional theory (DFT). The calculation results show that the V3Cl8 monolayer is an intrinsic anti-ferromagnetic semiconductor (AFS) with an indirect bandgap of 0.086 eV at the PBE functional level, while the V3X8 (X = F, Br, I) monolayer exhibits a fascinating ferromagnetic half-metal (FH) property with 100% spin-polarization at the Fermi level. Such 2D materials possess robust dynamical stability as well as thermal stability at room temperature except for V3Br8. In addition, Monte Carlo simulations based on the Ising model with the classical Heisenberg model estimate a Curie temperature of approximately 77 K and 103 K for the V3F8 and V3I8 systems, respectively. Furthermore, we predict an extraordinary phenomenon induced by biaxial compressive strain from the ferromagnetic half-metal (FH) to the ferromagnetic semiconductor (FS) at 2% strain and then to the antiferromagnetic metal (AM) with the biaxial strain increasing up to about 6.3% in the 2D V3I8 monolayer. In the case of 2D V3F8, as the strain varies from -10% to 8%, a series of electronic and magnetic phase transitions of AFS-AM-FH-AFS will occur. These tunable magnetic and electronic properties of 2D halides originate from the competition between AFM direct nearest-neighbor d-d exchange and FM superexchange via halogen p states, which leads to a variety of magnetic states. The explored controllable magnetic properties, electronic properties and the high Curie temperature render the 2D V3I8 monolayer a promising candidate for applications in magnetic logic devices and strain sensor devices.

Premartensitic transition and relevant magnetic effects in Ni50Mn34In15.5Al0.5 alloy.

Resistance measurement, in situ optical microscopic observation, thermal and magnetic measurements have been carried out on Ni50Mn34In15.5Al0.5 alloy. The existence of a pronounced premartensitic transition prior to martensitic transition can be characterized by microstructure evolution as well as exothermic peak and smooth decrease of resistance and magnetization with obvious hysteresis over a wide temperature range upon cooling. Consequently, the alloy undergoes two successive magneto-structural transitions consisting of premartensitic and martensitic transitions. Magnetoelastic coupling between magnetic and structural degrees of freedom would be responsible for the appearance of premartensitic transition, as evinced by the distinct shift of transitions temperatures to lower temperature with external applied field of 50 kOe. The inverse premartensitic transition induced by magnetic field results in large magnetoresistance, and contributes to the enhanced inverse magnetocaloric effect through enlarging the peak value and temperature interval of magnetic entropy change ΔSm.

Positive to negative zero-field cooled exchange bias in La0.5Sr0.5Mn0.8Co0.2O3 ceramics.

Exchange bias effect obtained after zero-field cooling from unmagnetized state usually exhibits a shift of hysteresis loop negative to the direction of the initial magnetic field, known as negative zero-field cooled exchange bias. Here, positive zero-field cooled exchange bias is reported in La0.5Sr0.5Mn0.8Co0.2O3 ceramics. In addition, a transition from positive to negative exchange bias has been observed with increasing initial magnetization field and measurement temperature. Based on a simple spin bidomain model with variable interface, two type of interfacial spin configuration formed during the initial magnetization process are proposed to interpret the observed phenomenon.

Significance of serum potassium level monitoring during the course of post-operative rehabilitation in patients with hypokalemia.

OBJECTIVE: Our objective was to evaluate the significance of pre-hospital and post-operative serum potassium level monitoring and hypokalemia intervention in laparotomy patients with hypokalemia. METHOD: A total of 118 laparotomy patients with hypokalemia were randomly divided into an intervention group (N = 60) and a control group (N = 58). Blood samples were collected for measurement of potassium levels at various time points (pre-admission, admission, 24 h and 48 h post-operation) for both groups. Hypokalemia interventions were administered to patients in the intervention group in the pre-admission period and the post-operative period. Visceral dynamics were assessed after laparotomy in both groups. RESULT: Average serum potassium levels at admission, time period of drinking, and time of first bowel sound after laparotomy differed significantly (p < 0.001) between the two groups. Average serum potassium levels, first time of defecation, urination, and ambulation at 24 h and 48 h post-operation differed significantly (p < 0.05) between the two groups. CONCLUSION: An optimal pathway of serum potassium monitoring not only saves limited ward space but also allows for early correction of hypokalemia in patients undergoing laparotomy.