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.

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.

Stretchable photothermal membrane of NIR-II charge-transfer cocrystal for wearable solar thermoelectric power generation.

Harvesting sunlight into cost-effective electricity presents an enticing prospect for self-powered wearable applications. The photothermal materials with an extensive absorption are fundamental to achieve optical and thermal concentration of the sunlight for efficiency output electricity of wearable solar thermoelectric generators (STEGs). Here, we synthesize an organic charge-transfer (CT) cocrystal with a flat absorption from ultraviolet to second near-infrared region (200 to 1950 nanometers) and a high photothermal conversion efficiency (PCE) of 80.5%, which is introduced into polyurethane toward large-area nanofiber membrane by electrospinning technology. These corresponding membranes demonstrate a high PCE of 73.7% under the strain more than 80%. Sandwiched with carbon nanotube-based thermoelectric fibers, the membranes as stretchable solar absorbers of STEGs could supply a notably increase temperature gradient, processing a maximum output voltage density of 23.4 volts per square meter at 1:00 p.m. under sunlight. This strategy presents an important insight in heat management for wearable STEGs with a desired electricity output.

Organic Bilayer Heterostructures with Built-In Exciton Conversion for 2D Photonic Encryption.

Organic multilayer heterostructures with accurate spatial organization demonstrate strong light-matter interaction from excitonic responses and efficient carrier transfer across heterojunction interfaces, which are considered as promising candidates toward advanced optoelectronics. However, the precise regulation of the heterojunction surface area for finely adjusting exciton conversion and energy transfer is still formidable. Herein, organic bilayer heterostructures (OBHs) with controlled face-to-face heterojunction via a stepwise seeded growth strategy, which is favorable for efficient exciton propagation and conversion of optical interconnects are designed and synthesized. Notably, the relative position and overlap length ratio of component microwires (LDSA /LBPEA = 0.39-1.15) in OBHs are accurately regulated by modulating the crystallization time of seeded crystals, resulting into a tailored heterojunction surface area (R = Loverlap /LBPEA = 37.6%-65.3%). These as-prepared OBHs present the excitation position-dependent waveguide behaviors for optical outcoupling characteristics with tunable emission colors and intensities, which are applied into two-dimensional (2D) photonic barcodes. This strategy opens a versatile avenue to purposely design OBHs with tailored heterojunctions for efficient energy transfer and exciton conversion, facilitating the application possibilities of advanced integrated optoelectronics.

Intervertebral Disc Progenitors: Lessons Learned from Single-Cell RNA Sequencing and the Role in Intervertebral Disc Regeneration.

The tremendous personal and economic burden worldwide caused by low back pain (LBP) has been surging in recent years. While intervertebral disc degeneration (IVDD) is the leading cause of LBP and vast efforts have been made to develop effective therapies, this problem is far from being resolved, as most treatments, such as painkillers and surgeries, mainly focus on relieving the symptoms rather than reversing the cause of IVDD. However, as stem/progenitor cells possess the potential to regenerate IVD, a deeper understanding of the early development and role of these cells could help to improve the effectiveness of stem/progenitor cell therapy in treating LBP. Single-cell RNA sequencing results provide fresh insights into the heterogeneity and development patterns of IVD progenitors; additionally, we compare mesenchymal stromal cells and IVD progenitors to provide a clearer view of the optimal cell source proposed for IVD regeneration.

Organic Charge-Transfer Cocrystals toward Large-Area Nanofiber Membrane for Photothermal Conversion and Imaging.

Organic photothermal materials integrating a high-efficiency light-heat conversion effect and high flexibility have generated immense interest in fundamental research and practical applications. Nevertheless, their practical applications still remain a challenge, owing to the complicated design, tedious synthesis, and limited programmable substrates. Herein, an organic charge-transfer cocrystal with a narrow energy gap of 0.33 eV and a high photothermal conversion efficiency (PCE) of 69.3% was rationally designed and synthesized via a facile self-assembly process, which was introduced into polyurethane for forming a large-area photothermal nanofiber membrane via electrospinning technology. Femtosecond transient absorption spectroscopy elucidates that the excellent PCE is attributed to the nonradiation transition process, including internal conversion and charge dissociation processes. Furthermore, the temperature of the as-prepared photothermal nanofiber membrane could quickly rise to 52 °C under laser irradiation with a power density of 0.183 W/cm2, suggesting a high PCE of 53.7%. This work successfully achieves the fabrication of a large-area photothermal membrane and the development of photothermal imaging.

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-specific multisystem disease as well as an important cause of maternal and perinatal death. This study aimed to analyze the placental transcriptional data and clinical information of PE patients available in the published database and predict the target genes for prevention of PE. METHODS: The clinical information and corresponding RNA data of PE patients were downloaded from the GEO database. Cluster analysis was performed to examine the correlation between different genotyping genes and clinical manifestations. Then, bioinformatic approaches including GO, KEGG, WGCNA, and GSEA were employed to functionally characterize candidate target genes involved in pathogenesis of PE. RESULTS: Two PE datasets GSE60438 and GSE75010 were obtained and combined, thereby providing the data of 205 samples in total (100 non-PE and 105 PE samples). After eliminating the batch effect, we grouped and analyzed the integrated data, and further performed GSEA analysis. It was found that the genes in group 1 and group 2 were different from those in normal samples. Moreover, WGCNA analysis revealed that genes in group 1 were up-regulated in turquoise module, including SASH1, PIK3CB and FLT-1, while genes in group 2 were up-regulated in the blue and brown modules. We further conducted GO and KEGG pathway enrichment analyses and found that the differential genes in turquoise module were mainly involved in biological processes such as small molecular catabolic process, while being highly enriched in pathways, including MAPK signaling pathway and Rap1 signaling pathway. CONCLUSION: FLT-1 was conventionally used to predict PE risk, and sFLT-1 could also be used as an indicator to evaluate PE treatment effect. As a candidate biomarker for predicting PE, SASH1 may participate in proliferation, migration, invasion and epithelial mesenchymal transformation of human trophoblast cells by regulating MAPK pathway and Rap1 signaling pathway, thus affecting the progression of PE. The mechanism allowing PIK3CB to regulate PE development was not clear, while the gene could be another candidate biomarker for PE risk prediction. This is an exploratory study and our findings were still required verification in further studies.

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.

Chinese herbal medicine Du-Huo-Ji-Sheng-decoction for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: As a classic prescription for treating knee osteoarthritis, Du-Huo-Ji-Sheng-decoction has been widely recognized for its clinical efficacy. The purpose of this systematic review and meta-analysis is to evaluate the effectiveness and safety of Du-Huo-Ji-Sheng-decoction in the treatment of knee osteoarthritis. METHODS: The following databases will be searched from January 2011 to December 2020: PubMed, Embase, Web of Science, Cochrane Library, Chinese Biomedical Medical Database, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and Wanfang Database. Statistical analysis will be processed by RevMan V.5.3 software. RESULTS: This study will provide an assessment of the current state of DHJSD in the treatment of KOA, aiming to show the efficacy and safety of DHJSD. CONCLUSION: This study will provide evidence to judge whether DHJSD is an effective intervention for KOA.

Chinese medicine NeuroAiD efficacy stroke recovery-extension study (CHIMES-E study): an observational multicenter study to investigate the longer-term efficacy of NeuroAiD in stroke recovery.

BACKGROUND: Stroke carries a poor long-term prognosis for death and disability. There are few acute treatments that reduce death and disability after stroke. The ongoing international, multicenter, randomized, placebo-controlled, double-blind CHIMES trial is currently testing the hypothesis that a 3-month course of the traditional Chinese medicine MLC601 (NeuroAiD) is superior to placebo in reducing neurological deficit and improving functional outcome after acute ischemic stroke in patients receiving standard stroke care. This extension study tests the hypothesis that at 2 years, an initial 3-month administration of NeuroAiD is superior to placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity. METHODS: Study subjects will be those who are already participants in CHIMES - aged above 21 years, had signs and symptoms of acute stroke, 6 ≤ NIHSS ≤ 14, neuroimaging consistent with ischemic stroke, and received study medication within 72 h of stroke onset. A subject will not be eligible for inclusion in CHIMES-E if they have withdrawn consent from all participation and follow-up for CHIMES. Subjects will be contacted at 6, 12, 18 and 24 months after CHIMES enrollment. After verbal consent is obtained, subjects will be assessed for functional state by the modified Rankin scale (mRS) and Barthel Index (BI), and a history of recurrent vascular events as well as medical events. The primary outcome measure will be the mRS at month 24. Secondary outcome measures will be mRS and BI at 6, 12 and 18 months, and BI at 24 months. Analysis will be based on the intention-to-treat principle. If the number of patients lost to follow-up is substantial, a sensitivity analysis based on the last observation carried forward method will be carried out, to compare the results with those from the main analysis without imputation. Based on a cumulative odds ratio of 1.5 for the NeuroAiD group, a two-sided test of 5% type I error and an expected 30% dropout rate after 2 years of follow-up for the 1,100 patients recruited into CHIMES, the 770 subjects with mRS data expected to be available at year 2 yields an 89% power to detect a difference in efficacy between NeuroAiD and placebo. CONCLUSIONS: This study will provide evidence for the longer-term efficacy of an initial course of a neurorestorative therapy after acute ischemic stroke of intermediate severity.

The effectiveness of dual antiplatelet treatment in acute ischemic stroke patients with intracranial arterial stenosis: a subgroup analysis of CLAIR study.

BACKGROUND: Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction (CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease. METHODS: CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis. RESULTS: There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two (P = 0·043) and day seven (P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4-79·6; P = 0·036) and number (adjusted mean difference -0·9; 95% confidence interval -1·5 to -0·3; P = 0·004) of positive emboli at day seven. CONCLUSIONS: Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis.

A comparison of the Supreme laryngeal mask airway with the Proseal laryngeal mask airway in anesthetized paralyzed adult patients: a randomized crossover study.

PURPOSE: The Supreme laryngeal mask airway (SLMA) is a new single-use advanced form of the Proseal laryngeal mask airway (PLMA). This study tested the hypothesis that the SLMA is equally as effective as the PLMA as a supraglottic ventilatory device in anesthetized paralyzed adult patients. METHODS: Size 4 SLMAs and PLMAs were compared in a randomized crossover study involving 60 patients aged 21-75 yr and American Society of Anesthesiologists physical status I and II. Once the patients were anesthetized and paralyzed, the SLMA and the PLMA were inserted into each patient in random order. The primary outcome measure was the laryngeal seal pressure (LSP) at an intracuff pressure of 60 cm H(2)O. Secondary outcome measures included the ease of inserting the laryngeal mask airway devices (LMADs) and the fibreoptic position of the airway tube. RESULTS: There was no statistically significant difference in LSP between the SLMA and the PLMA. The mean LSP was 19.6 +/- 5.8 cm H(2)O and 20.9 +/- 6.7 cm H(2)O for the SLMA and the PLMA, respectively. There was a similarity between the SLMA and the PLMA regarding the number of attempts required and the duration for insertion. However, fibreoptic positioning was better with the PLMA than with the SLMA (P < 0.0001). CONCLUSION: The clinical performance of the SLMA as a ventilatory device is comparable with that of the PLMA, as illustrated by the similar LSPs. The inferior position of the SLMA airway tube compared with that of the PLMA does not affect its ease of ventilation.