Comparative efficacy and safety of JAK/TYK2 inhibitors and other oral drugs for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis.

Background Janus kinase (JAK)/tyrosine kinase 2 (TYK2) inhibitors are novel treatments for moderate-to-severe plaque psoriasis. Objective To perform a network meta-analysis to compare the efficacy and safety of TYK2 inhibitors with other oral drugs in moderate-to-severe psoriasis. Methods Eligible randomised clinical trials (RCTs) were identified from public databases (published before November 2, 2023). Random-effect frequentist network meta-analysis was performed with ranking based on the surface under the cumulative ranking curve (SUCRA) of Physician's Global Assessment of "clear" or "almost clear" (PGA 0/1), 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75). Results Twenty RCTs containing 7,564 patients with moderate-to-severe psoriasis were included. Deucravacitinib at all dose levels (except for 3 mg every other day) and tofacitinib (10 mg BID) ranked best in achieving PGA 0/1 and PASI-75 at 12- 16 weeks. Tofacitinib (10 mg BID) was considered the most unsafe. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Limitations Insufficiency of eligible data and no long-term follow-up data. Conclusion Deucravacitinib showed superior efficacy and safety for treating moderate-to-severe psoriasis over other included drugs.

Successful treatment of classic Kaposi sarcoma with Trichophyton rubrum-infected onychomycosis and tinea pedis utilizing combination of oral itraconazole and thalidomide.

Kaposi sarcoma (KS) is a vascular proliferative tumor caused by human herpesvirus 8. At present, the treatment of KS is difficult and refractory. Here, we report a 68-year-old man who was diagnosed with a classical KS with tinea pedis and onychomycosis, infected by Trichophyton rubrum, and treated with itraconazole and thalidomide after locational excision of several bigger nodules. The lesions were relieved during treatment, and recurred after discontinuation. Retreatment still achieved good effect and the therapy was tapered down after control. After the whole course of treatment, the skin lesions subsided significantly without obvious adverse reactions, which showed that itraconazole combined with thalidomide may be another effective and safe treatment for KS in some cases.

Effects of autonomic nervous system disorders on male infertility.

The male reproductive functions are largely regulated by the autonomic nervous system. Male sexual behavior and fertility primarily depend on the normal function of the higher neural centers related to the autonomic nervous system, the hypothalamic-pituitary-gonadal axis, the autonomic nervous components within the spinal cord and spinal nerves, and certain somatic nerves in the pelvic floor. In this review article, we will summarize the role of the autonomic nervous system in regulating male reproductive capabilities and fertility, its impact on male infertility under abnormal conditions, including the role of drug-induced autonomic nervous dysfunctions on male infertility. The main purpose of this article was to provide an overview of the effects of autonomic nervous dysfunction on male reproductive function and shed light on the potential therapeutic target for male infertility.

Multifunctional Actuator Based on Graphene/PDMS Composite Materials with Shape Programmable Configuration and High Photothermal Conversion Capability.

Photoresponsive smart actuators based on carbon materials are attracting increasing attention. However, the low content of carbon materials currently limits the development of carbon material actuators. In this work, we designed and prepared a multifunctional bilayer composite actuator with controllable structures and high photothermal conversion efficiency. The actuator consists of a graphene/polydimethylsiloxane (PDMS) composite layer and a PDMS layer. With an ultrahigh graphene mass fraction (30%), the actuator exhibits a good hydrophobicity, unexpectedly high photothermal conversion performance (from room temperature to 120 °C within 1 s), and rapid photo-response capability. By thermal regulation, ultraviolet laser cutting, and assembly, the actuator can achieve shape programmable configuration in three-dimensional directions. Bionic crawling robots achieve a crawling speed of 0.065 mm/s, and liquid tracking robots achieve a rotational motion of 106°/s, a linear motion of 8.42 mm/s, and a complex "W"-shaped trajectory motion. This work provides a simple and effective method for the preparation and realization of multifunctional actuators based on graphene composite materials.

Pressure-Strengthened Carbon Fibers from Mesophase Pitch Carbonization Processes.

Little attention has been devoted to studying the pressures during the mesophase pitches carbonization processes and their effects on the as-produced carbon fibers' mechanical properties. Herein, we study the pressure-enhanced graphitization of mesophase pitch and the promoted tensile stresses of the produced carbon fibers using full atomistic simulations based on reactive force fields. Results show that pressures increase the tensile stress of as-produced fibers by 3.7-11 times under 1-6 GPa isotropic compressing pressure. The highest tensile stress can reach 4.39 GPa in carbonized coal tar pitch at 4000 K under 6 GPa. In experimental work, the pressurized laser-processed mesophase pitch generates less gas and shows more ordered carbonized structures in Raman spectra. This work provides a fundamental understanding of the reaction mechanism of carbon fiber production under pressure, and also illustrates a promising method to manufacture mesophase pitch-based carbon fibers with exceptional mechanical properties.

Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts.

Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD). Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo's myocardial protective effect. Joint application of two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF MS identified eight differentially expressed proteins between groups. Expression of cardiac succinate dehydrogenase (ubiquinone) flavoprotein subunit (SDHA) increased more than two-fold after I/R, while IPo led to overexpression of dihydrolipoyl dehydrogenase (DLD), NADH dehydrogenase (ubiquinone) flavoprotein 1 and isoform CRA_b (NDUFV1). When the mitoKATP was blocked, MICOS complex subunit Mic60 (IMMT) and Stress-70 protein (Grp75) were over expressed, while DLDH, ATPase subunit A (ATPA) and rCG44606 were decreased. Seven of the differential proteins belong to electron transport chain (ETC) or metabolism regulating proteins, and five of them were induced by closing mitoKATP in I/R hearts. We thus conclude that IPo's myocardial protective effect relies on energy homeostasis regulation. DLD, SDHA, NDUFV1, Grp75, ATPA and rCG44606 may contribute to IPo's cardial protective effect.

Effect of Tween 40 and DtsR1 on L-arginine overproduction in Corynebacterium crenatum.

BACKGROUND: L-Glutamate is an important precursor in the L-arginine (L-Arg) biosynthetic pathway. Various methods, including polyoxyethylene sorbitan monopalmitate (Tween 40) addition and dtsR1 disruption, have been widely used to induce L-glutamate overproduction in Corynebacterium glutamicum. In this study, a novel strategy for L-Arg overproduction through Tween 40 trigger and ΔdtsR1 mutant were proposed in Corynebacterium crenatum. RESULTS: Corynebacterium crenatum mutant (CCM01) was selected as a host strain, whose argR was lethal via mutagenesis screening, the proB gene was knocked out, and argB was replaced by argB M4 (E19R, H26E, D311R, and D312R) to release L-Arg feedback resistance. After Tween 40 trigger in the logarithmic period, L-Arg production increased from 15.22 to 17.73 g/L in CCM01 strain. When NCgl1221 and dtsR1 disruption (CCM03), L-Arg production drastically increased to 27.45 g/L and then further to 29.97 g/L after Tween 40 trigger. Moreover, the specific activity of α-oxoglutarate dehydrogenase complex (ODHC) decreased, whereas the regeneration of NADP(+)/NADPH significantly increased after dtsR1 disruption and Tween 40 trigger. Results of real-time PCR showed that the transcriptional levels of odhA, sucB, and lpdA (encoding three subunits of the ODHC complex) were downregulated after Tween 40 trigger or dtsR1 disruption. By contrast, zwf transcription (encoding glucose-6-phosphate dehydrogenase) showed no significant difference among CCM01, CCM02 (ΔNCgl1221), and CCM03 (ΔNCgl1221ΔdtsR1) strains without Tween 40 trigger but evidently increased by 5.50 folds after Tween 40 trigger. CONCLUSION: A novel strategy for L-Arg overproduction by dtsR1 disruption and Tween 40 trigger in C. crenatum was reported. Tween 40 addition exhibited a bifunctional mechanism for L-Arg overproduction, including reduced ODHC activity and enhanced NADPH pools accumulation by downregulated dtsR1 expression and upregulated zwf expression, respectively.