Hydrophilic 1T-WS2 Nanosheet Arrays toward Conductive Textiles for High-Efficient and Continuous Hydroelectric Generation and Storage.

Flexible hydroelectric generators (HEGs) are promising self-powered devices that spontaneously derive electrical power from moisture. However, achieving the desired compatibility between a continuous operating voltage and superior current density remains a significant challenge. Herein, a textile-based van der Waals heterostructure is rationally designed between conductive 1T phase tungsten disulfide@carbonized silk (1T-WS2@CSilk) and carbon black@cotton (CB@Cotton) fabrics with an asymmetric distribution of oxygen-containing functional groups, which enhances the proton concentration gradients toward high-performance wearable HEGs. The vertically staggered 1T-WS2 nanosheet arrays on the CSilk fabric provide abundant hydrophilic nanochannels for rapid carrier transport. Furthermore, the moisture-induced primary battery formed between the active aluminum (Al) electrode and the conductive textiles introduces the desired electric field to facilitate charge separation and compensate for the decreased streaming potential. These devices exhibit a power density of 21.6 µW cm-2, an open-circuit voltage (Voc) of 0.65 V sustained for over 10 000 s, and a current density of 0.17 mA cm-2. This performance makes them capable of supplying power to commercial electronics and human respiratory monitoring. This study presents a promising strategy for the refined design of wearable electronics.

Viral and Host Transcriptomes in SARS-CoV-2-Infected Human Lung Cells.

Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.

Ethylene-induced stomatal closure is mediated via MKK1/3-MPK3/6 cascade to EIN2 and EIN3.

Mitogen-activated protein kinases (MPKs) play essential roles in guard cell signaling, but whether MPK cascades participate in guard cell ethylene signaling and interact with hydrogen peroxide (H2 O2 ), nitric oxide (NO), and ethylene-signaling components remain unclear. Here, we report that ethylene activated MPK3 and MPK6 in the leaves of wild-type Arabidopsis thaliana as well as ethylene insensitive2 (ein2), ein3, nitrate reductase1 (nia1), and nia2 mutants, but this effect was impaired in ethylene response1 (etr1), nicotinamide adenine dinucleotide phosphate oxidase AtrbohF, mpk kinase1 (mkk1), and mkk3 mutants. By contrast, the constitutive triple response1 (ctr1) mutant had constitutively active MPK3 and MPK6. Yeast two-hybrid, bimolecular fluorescence complementation, and pull-down assays indicated that MPK3 and MPK6 physically interacted with MKK1, MKK3, and the C-terminal region of EIN2 (EIN2 CEND). mkk1, mkk3, mpk3, and mpk6 mutants had typical levels of ethylene-induced H2 O2 generation but impaired ethylene-induced EIN2 CEND cleavage and nuclear translocation, EIN3 protein accumulation, NO production in guard cells, and stomatal closure. These results show that the MKK1/3-MPK3/6 cascade mediates ethylene-induced stomatal closure by functioning downstream of ETR1, CTR1, and H2 O2 to interact with EIN2, thereby promoting EIN3 accumulation and EIN3-dependent NO production in guard cells.

Identification of differentially expressed miRNA 48 h after cerebral ischemia-reperfusion injury in mice by the technique of miRNA microarray.

The objective was to identify the differential expressed miRNA during cerebral ischemia-reperfusion injury (CIRI) process, thereby assisting in elucidating the mechanism of CIRI development and providing a potential target for CIRI prevention and treatment. Six mice were randomly assigned to two groups: control group and CIRI model group. A global cerebral IR model by four-vessel occlusion was prepared among the CIRI model group. Brain tissues were collected 48 h after reperfusion. Total RNA was extracted for each sample. miRNA microarrays were employed to detect the differentially expressed miRNA between the CIRI group and the control group. One differentially expressed miRNA was selected for verification by PCR. Compared with the control group, 69 miRNAs were significantly differential expressed in samples of the CIRI group, among which 50 miRNAs were upregulated and 19 miRNAs were downregulated. The real-time qPCR results indicated that the results of the miRNA microarray were reliable. A number of miRNAs were significantly regulated in the CIRI model, which suggested that miRNA was closely associated with the pathological alterations after ischemia. These identified miRNAs may provide directions and targets for the future pathological research of CIRI.

Post hoc analysis of a randomised, placebo-controlled, active-reference 6-week study of brexpiprazole in acute schizophrenia.

OBJECTIVE: We provide a closer look at the result of a randomised, placebo-controlled, active-reference (quetiapine XR), flexible-dose, 6-week study of brexpiprazole in schizophrenia, which did not meet its primary endpoint - change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. We also investigate potential expectancy bias from the well-known side-effect profile of the active reference that could have affected the study outcome. METHODS: Pre-specified sensitivity analyses of the primary end point were performed using analysis of covariance (ANCOVA) last observation carried forward (LOCF) and observed cases (OC). Post hoc analyses of change from baseline in PANSS total score were performed using the mixed model for repeated measures approach with treatment groups split by having typical adverse events with potential for functional unblinding, for example, somnolence, increase in weight, dizziness, dry mouth and sedation. RESULTS: Pre-specified sensitivity analyses showed separation from placebo for brexpiprazole at week 6: LOCF, ANCOVA: -4.3 [95% CI (-8.0, -0.5), p = 0.0254]. OC, ANCOVA: -3.9 [95% CI (-7.3, -0.5), p = 0.0260]. Patients treated with brexpiprazole experiencing typical adverse events with potential for functional unblinding before or at Week 2 had a least square (LS) mean PANSS change of -29.5 (improvement), with a difference in change from baseline to Week 6 in PANSS total score between brexpiprazole and placebo of -13.5 [95% CI (-23.1, -4.0), p = 0.0057], and those who did not had an LS mean change of -18.9 and a difference between brexpiprazole and placebo of -2.9 [95% CI (-7.2, 1.4), p = 0.1809]. CONCLUSION: Pre-specified sensitivity analyses showed separation from placebo for brexpiprazole at Week 6. A post hoc analysis suggested a potential confounding of efficacy rating towards symptom improvement in patients who experience known side effects of quetiapine XR.

Searching for the optimal precondition procedure for mesenchymal stem/stromal cell treatment: Facts and perspectives.

Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies, and pretreatment has proven to enhance cell vitality and function. In a recent publication, Li et al explored a new combination of pretreatment conditions. Here, we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.

Fueling recovery: The importance of energy coupling between angiogenesis and osteogenesis during fracture healing.

Approximately half of bone fractures that do not heal properly (non-union) can be accounted to insufficient angiogenesis. The processes of angiogenesis and osteogenesis are spatiotemporally regulated in the complex process of fracture healing that requires a substantial amount of energy. It is thought that a metabolic coupling between angiogenesis and osteogenesis is essential for successful healing. However, how this coupling is achieved remains to be largely elucidated. Here, we will discuss the most recent evidence from literature pointing towards a metabolic coupling between angiogenesis and osteogenesis. We will describe the metabolic profiles of the cell types involved during fracture healing as well as secreted products in the bone microenvironment (such as lactate and nitric oxide) as possible key players in this metabolic crosstalk.

Macroscopic inhibition of DNA damage repair pathways by targeting AP-2α with LEI110 eradicates hepatocellular carcinoma.

DNA damage repair (DDR) genes are known to be closely associated with the progression of Hepatocellular carcinoma (HCC). Here we report a unique cluster of "deletion-up" genes in HCC, which are accordantly overexpressed in HCC patients and predict the unfavorable prognosis. Binding motif analysis and further validation with ChIP-qPCR unveil that the AP-2α directly modulate the transcription of critical DNA repair genes including TOP2A, NUDT1, POLD1, and PARP1, which facilitates the sanitation of oxidized DNA lesions. Structural analysis and the following validation identify LEI110 as a potent AP-2α inhibitor. Together, we demonstrate that LEI110 stabilizes AP-2α and sensitizes HCC cells toward DNA-damaging reagents. Altogether, we identify AP-2α as a crucial transcription modulator in HCC and propose small-molecule inhibitors targeting AP-2α are a promising novel class of anticancer agents. Our study provides insights into the concept of macroscopic inhibition of DNA damage repair-related genes in cancer treatment.

Tactile Sensing and Rendering Patch with Dynamic and Static Sensing and Haptic Feedback for Immersive Communication.

Wearable human-machine interface (HMI) with bidirectional and multimodal tactile information exchange is of paramount importance in teleoperation by providing more intuitive data interpretation and delivery of tactilely related signals. However, the current sensing and feedback devices still lack enough integration and modalities. Here, we present a Tactile Sensing and Rendering Patch (TSRP) that is made of a customized expandable array which consists of a piezoelectric sensing and feedback unit fused with an elastomeric triboelectric multidimensional sensor and its inner pneumatic feedback structure. The primary functional unit of TSRP is mainly featured with a soft silicone substrate with compact multilayer structure integrating static and dynamic multidimensional tactile sensing capabilities, which synergistically leverage both triboelectric and piezoelectric effects. Additionally, based on the air chamber created by the triboelectric sensor and the converse piezoelectric effect, it provides pneumatic and vibrational haptic feedback simultaneously for both static and dynamic perception regeneration. With the aid of the other variants of this unit, the array shaped TSRP is capable of simulating different terrains, geometries, sliding, collisions, and other critical interactive events during teleoperation via skin perception. Moreover, immediate manipulation can be done on TSRP through the tactile sensors. The preliminary demonstration of TSRP interface with a completed control module in robotic teleoperation is provided, which shows the feasibility of assisting certain tasks in a complex environment by direct tactile communication. The proposed device offers a potential method of enabling bidirectional tactile communication with enriched key information for improving interaction efficiency in the fields of robot teleoperation and training.

Acid leaching of vivianite separated from sewage sludge for recovering phosphorus and iron.

This paper examines the acid leaching efficiencies of Fe and P from vivianite slurry (VS, Fe3(PO4)2·8H2O), which is magnetically separated from anaerobic digested sludge, and elaborates on Fe and P reuse routes. The characteristics and dissolution behavior of raw VS in hydrochloric, sulfuric, phosphoric, oxalic, and citric acids are investigated. Results reveal that the primary impurities in VS are organic matter, other phosphate compounds, and Mg present in the vivianite crystal structure. Hydrochloric and sulfuric acids could effectively extract P (90%) from VS at an optimal hydrogen-to-phosphorus (H⁺/P) ratio of 2.5, compared with sewage sludge ash (SSA) that normally needs an H⁺/P ratio greater than 3. Hence, VS can be employed as an alternative P resource following a similar recovery route used with SSA. However, in comparison to SSA, VS use can decrease acid consumption in P extraction and the requirement for the extensive purification of cationic impurities. Furthermore, oxalic acid effectively facilitates the separation of P and Fe in VS by precipitating Fe as insoluble ferrous oxalate in acidic conditions, leading to a high Fe recovery rate of 95%. The recovery and reuse of Fe through the oxalic acid route further improves the feasibility of VS as an alternate resource.