Iron-catalyzed benzylic C-H thiolation via photoinduced ligand-to-metal charge-transfer.

Here, we describe an iron-catalyzed benzylic C-H thiolation of alkylarenes via photoinduced ligand-to-metal charge-transfer. The protocol features operational simplicity, mild reaction conditions, and the use of FeCl3 as catalyst and thiols/disulfides as sulfur sources, which enables the transformation of diverse benzylic C-H bonds into C-S bonds with a high efficiency.

Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

A study of the attenuation stage of a global infectious disease.

Introduction: Differences in control measures and response speeds between regions may be responsible for the differences in the number of infections of global infectious diseases. Therefore, this article aims to examine the decay stage of global infectious diseases. We demonstrate our method by considering the first wave of the COVID-19 epidemic in 2020. Methods: We introduce the concept of the attenuation rate into the varying coefficient SEIR model to measure the effect of different cities on epidemic control, and make inferences through the integrated adjusted Kalman filter algorithm. Results: We applied the varying coefficient SEIR model to 136 cities in China where the total number of confirmed cases exceeded 20 after the implementation of control measures and analyzed the relationship between the estimated attenuation rate and local factors. Subsequent analysis and inference results show that the attenuation rate is significantly related to the local annual GDP and the longitude and latitude of a city or a region. We also apply the varying coefficient SEIR model to other regions outside China. We find that the fitting curve of the average daily number of new confirmed cases simulated by the variable coefficient SEIR model is consistent with the real data. Discussion: The results show that the cities with better economic development are able to control the epidemic more effectively to a certain extent. On the other hand, geographical location also affected the effectiveness of regional epidemic control. In addition, through the results of attenuation rate analysis, we conclude that China and South Korea have achieved good results in controlling the epidemic in 2020.

A Wood-Derived Periosteum for Spatiotemporal Drug Release: Boosting Bone Repair through Anisotropic Structure and Multiple Functions.

Existing artificial periostea face many challenges, including difficult-to-replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood-derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA) binder layer, and layer-by-layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long-term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre-encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDA coating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.

Unraveling the role of PlARF2 in regulating deed formancy in Paeonia lactiflora.

MAIN CONCLUSION: PlARF2 can positively regulate the seed dormancy in Paeonia lactiflora Pall. and bind the RY cis-element. Auxin, a significant phytohormone influencing seed dormancy, has been demonstrated to be regulated by auxin response factors (ARFs), key transcriptional modulators in the auxin signaling pathway. However, the role of this class of transcription factors (TFs) in perennials with complex seed dormancy mechanisms remains largely unexplored. Here, we cloned and characterized an ARF gene from Paeonia lactiflora, named PlARF2, which exhibited differential expression levels in the seeds during the process of seed dormancy release. The deduced amino acid sequence of PlARF2 had high homology with those of other plants and contained typical conserved Auxin_resp domain of the ARF family. Phylogenetic analysis revealed that PlARF2 was closely related to VvARF3 in Vitis vinifera. The subcellular localization and transcriptional activation assay showed that PlARF2 is a nuclear protein possessing transcriptional activation activity. The expression levels of dormancy-related genes in transgenic callus indicated that PlARF2 was positively correlated with the contents of PlABI3 and PlDOG1. The germination assay showed that PlARF2 promoted seed dormancy. Moreover, TF Centered Yeast one-hybrid assay (TF-Centered Y1H), electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter assay analysis (Dual-Luciferase) provided evidence that PlARF2 can bind to the 'CATGCATG' motif. Collectively, our findings suggest that PlARF2, as TF, could be involved in the regulation of seed dormancy and may act as a repressor of germination.

Identification and Analysis of Human-Exoskeleton Coupling Parameters in Lower Extremities.

This paper proposed linear and non-linear models for predicting human-exoskeleton coupling forces to enhance the studies of human-exoskeleton coupling dynamics. Then the parameters of these models were identified with a newly designed platform and the help of ten adult male and ten adult female volunteers (Age: 23.65 ±4.03 years, Height: 165.60 ±8.32 mm, Weight: 62.35 ±14.09 kg). Comparing the coupling force error predicted by the models with experimental measurements, one obtained a more accurate and robust prediction of the coupling forces with the non-linear model. Moreover, statistical analysis of the experimental data was performed to reveal the correlation between the coupling parameters and coupling positions and looseness. Finally, backpropagation (BP) neural network and Gaussian Process Regression (GPR) were used to predict the human-exoskeleton coupling parameters. The significance of each input parameter to the human-exoskeleton coupling parameters was assessed by analyzing the sensitivity of GPR performance to its inputs. The novelty and contribution are the establishment of the non-linear coupling model, the design of the coupling experimental platform and a regression model which provides a possibility to obtain human-exoskeleton without experimental measurement and identification. Based on this work, one can optimize control algorithm and design comfortable human-exoskeleton interaction.

Climate Impacts of Hydrogen and Methane Emissions Can Considerably Reduce the Climate Benefits across Key Hydrogen Use Cases and Time Scales.

Recent investments in "clean" hydrogen as an alternative to fossil fuels are driven by anticipated climate benefits. However, most climate benefit calculations do not adequately account for all climate warming emissions and impacts over time. This study reanalyzes a previously published life cycle assessment as an illustrative example to show how the climate impacts of hydrogen deployment can be far greater than expected when including the warming effects of hydrogen emissions, observed methane emission intensities, and near-term time scales; this reduces the perceived climate benefits upon replacement of fossil fuel technologies. For example, for blue (natural gas with carbon capture) hydrogen pathways, the inclusion of upper-end hydrogen and methane emissions can yield an increase in warming in the near term by up to 50%, whereas lower-end emissions decrease warming impacts by at least 70%. For green (renewable-based electrolysis) hydrogen pathways, upper-end hydrogen emissions can reduce climate benefits in the near term by up to 25%. We also consider renewable electricity availability for green hydrogen and show that if it is not additional to what is needed to decarbonize the electric grid, there may be more warming than that seen with fossil fuel alternatives over all time scales. Assessments of hydrogen's climate impacts should include the aforementioned factors if hydrogen is to be an effective decarbonization tool.

NLRP3 deficiency protects against acetaminophen­induced liver injury by inhibiting hepatocyte pyroptosis.

Acetaminophen (APAP) overdose is the primary cause of drug­induced acute liver failure in numerous Western countries. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation serves a pivotal role in the pathogenesis of various forms of acute liver injury. However, the cellular source for NLRP3 induction and its involvement during APAP­induced hepatotoxicity have not been thoroughly investigated. In the present study, hematoxylin and eosin staining was performed to assess histopathological changes of liver tissue. Immunohistochemistry staining(NLRP3, Caspase­1, IL­1ß, GSDMD and Caspase­3), western blotting (NLRP3, Caspase­1, IL­1ß, GSDMD and Caspase­3) and RT­qPCR (NLRP3, Caspase­1 and IL­1ß) were performed to assess the expression of NLRP3/GSDMD signaling pathway. TUNEL staining was performed to assess apoptosis of liver tissue. The serum expression levels of inflammatory factors (IL­6, IL­18, IL­1ß and TNF­α) were assessed using ELISA and inflammation of liver tissue was assessed using immunohistochemistry (Ly6G and CD68) and RT­qPCR (TNF­α, Il­6, Mcp­1, Cxcl­1, Cxcl­2). A Cell Counting Kit­8 was performed to assess cell viability and apoptosis. Protein and gene expression were analyzed by western blotting (PCNA, CCND1) and RT­qPCR (CyclinA2, CyclinD1 and CyclinE1). Through investigation of an APAP­induced acute liver injury model (AILI), the present study demonstrated that APAP overdose induced activation of NLRP3 and cleavage of gasdermin D (GSDMD) in hepatocytes, both in vivo and in vitro. Additionally, mice with hepatocyte­specific knockout of Nlrp3 exhibited reduced liver injury and lower mortality following APAP intervention, accompanied by decreased infiltration of inflammatory cells and attenuated inflammatory response. Furthermore, pharmacological blockade of NLRP3/GSDMD signaling using MCC950 or disulfiram significantly ameliorated liver injury and reduced hepatocyte death. Notably, hepatocyte Nlrp3 deficiency promoted liver recovery by enhancing hepatocyte proliferation. Collectively, the present study demonstrated that inhibition of the NLRP3 inflammasome protects against APAP­induced acute liver injury by reducing hepatocyte pyroptosis and suggests that targeting NLRP3 may hold therapeutic potential for treating AILI.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2 , hospitalized and received supplemental O2 , admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Adipose-derived stem cells in immune-related skin disease: a review of current research and underlying mechanisms.

Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell-cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell-cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.

A Versatile Approach for the Synthesis of Antimicrobial Polymer Brushes on Natural Rubber/Graphene Oxide Composite Films via Surface-Initiated Atom-Transfer Radical Polymerization.

A simple strategy was adopted for the preparation of an antimicrobial natural rubber/graphene oxide (NR/GO) composite film modified through the use of zwitterionic polymer brushes. An NR/GO composite film with antibacterial properties was prepared using a water-based solution-casting method. The composited GO was dispersed uniformly in the NR matrix and compensated for mechanical loss in the process of modification. Based on the high bromination activity of α-H in the structure of cis-polyisoprene, the composite films were brominated on the surface through the use of N-bromosuccinimide (NBS) under the irradiation of a 40 W tungsten lamp. Polymerization was carried out on the brominated films using sulfobetaine methacrylate (SBMA) as a monomer via surface-initiated atom transfer radical polymerization (SI-ATRP). The NR/GO composite films modified using polymer brushes (PSBMAs) exhibited 99.99% antimicrobial activity for resistance to Escherichia coli and Staphylococcus aureus. A novel polymer modification strategy for NR composite materials was established effectively, and the enhanced antimicrobial properties expand the application prospects in the medical field.

Defense Responses of Different Rice Varieties Affect Growth Performance and Food Utilization of Cnaphalocrocis medinalis Larvae.

Rice leaf folder, Cnaphalocrocis medinalis (Guenée), is one of the most serious pests on rice. At present, chemical control is the main method for controlling this pest. However, the indiscriminate use of chemical insecticides has non-target effects and may cause environmental pollution. Besides, leaf curling behavior by C. medinalis may indirectly reduce the efficacy of chemical spray. Therefore, it is crucial to cultivate efficient rice varieties resistant to this pest. Previous studies have found that three different rice varieties, Zhongzao39 (ZZ39), Xiushui134 (XS134), and Yongyou1540 (YY1540), had varying degrees of infestation by C. medinalis. However, it is currently unclear whether the reason for this difference is related to the difference in defense ability of the three rice varieties against the infestation of C. medinalis. To explore this issue, the current study investigated the effects of three rice varieties on the growth performance and food utilization capability of the 4th instar C. medinalis. Further, it elucidated the differences in defense responses among different rice varieties based on the differences in leaf physiological and biochemical indicators and their impact on population occurrence. The results showed that the larval survival rate was the lowest, and the development period was significantly prolonged after feeding on YY1540. This was not related to the differences in leaf wax, pigments, and nutritional components among the three rice varieties nor to the feeding preferences of the larvae. The rate of superoxide anion production, hydrogen peroxide content, and the activity of three protective enzymes were negatively correlated with larval survival rate, and they all showed the highest in YY1540 leaves. Compared to other tested varieties, although the larvae feeding on YY1540 had higher conversion efficiency of ingested food and lower relative consumption rate, their relative growth was faster, indicating stronger food utilization capability. However, they had a lower accumulation of protein. This suggests that different rice varieties had different levels of oxidative stress after infestation by C. medinalis. The defense response of YY1540 was more intense, which was not conducive to the development of the larvae population. These results will provide new insights into the interaction mechanism between different rice varieties and C. medinalis and provide a theoretical basis for cultivating rice varieties resistant to this pest.

scDesign3 generates realistic in silico data for multimodal single-cell and spatial omics.

We present a statistical simulator, scDesign3, to generate realistic single-cell and spatial omics data, including various cell states, experimental designs and feature modalities, by learning interpretable parameters from real data. Using a unified probabilistic model for single-cell and spatial omics data, scDesign3 infers biologically meaningful parameters; assesses the goodness-of-fit of inferred cell clusters, trajectories and spatial locations; and generates in silico negative and positive controls for benchmarking computational tools.

Effects of acupoints-based TENS combined with tDCS on spasticity and motor function in ischemic stroke with spastic hemiplegia: study protocol for a randomized controlled trial.

Background: Spastic hemiplegia following ischemic strokes seriously impedes the recovery of motor function posing a vast rehabilitation challenge. As the uncertain effects of recommended conventional treatments such as botulinum toxin injections on active functional improvement and potential adverse effects cannot be bypassed, there is an increasing need in alternative, more effective and safer modalities. Acupoints-based transcutaneous electrical nerve stimulation (Acu-TENS) and transcranial direct current stimulation (tDCS) are effective non-invasive modalities for stroke rehabilitation, particularly showing anti-spastic effect and functional improvements as well. However, the optimal stimulation frequency of Acu-TENS and whether combination of Acu-TENS and tDCS exert synergistic effect remain to be investigated. Objective: To evaluate the effects of Acu-TENS combined with tDCS on spasticity and motor function in ischemic stroke patients with spastic hemiplegia and screen the optimal frequency of Acu-TENS. Methods: A total of 90 post-ischemic stroke patients with spastic hemiplegia will be intervened for 4 weeks and followed up for 4 weeks. They will be randomly assigned to three groups including two observation groups and a standard care control group in a 1:1:1 ratio. All patients will receive standard care and regular rehabilitation accordingly. In addition, the two observation groups will receive 12 sessions of Acu-TENS at 20 Hz or 100 Hz for 30 min combined with 1 mA tDCS for 20 min, three times a week, for 4 weeks. The primary outcome is the change in total modified Ashworth scale (MAS) score from baseline to week 4. Secondary outcomes include changes in surface electromyography (SEMG), Fugl-Meyer Motor Function Scale, Modified Barthel Index (MBI), and 10-meter walk test from baseline to week 4. MAS score will also be measured after 4 weeks of follow-up. Adverse events throughout the study will be recorded. Discussion: This trial will evaluate, for the first time, the therapeutic potentials and safety of Acu-TENS combined with tDCS on spasticity and motor function in stroke patients. It will provide evidence for frequency-dependent anti-spastic effect of Acu-TENS, and a reference for rated parameter setting of new mixed transcutaneous and transcranial stimulation system for stroke rehabilitation, thereby promoting proactive healthcare consequently. Trial registration: Chinese Clinical Trials Register ChiCTR2200067186.

Preparation and Self-Cleaning Performance of High-Strength Double-Layer PVDF-PVC-Nano-Graphite/PVDF-PVC Super-Hydrophobic Composite Membrane.

The double-layer PVDF-PVC (D-PP/PP) super-hydrophobic composite membrane was prepared by the coating immersion phase separation method to enhance the mechanical properties of the composite membrane. The D-PP/PP super-hydrophobic membrane was prepared using the casting solution concentration of 12 wt% PVDF-PVC composite membrane as basement and 4% casting of PVDF-PVC coating. The contact angle of the D-PP/PP membrane was 150.4 ± 0.3°, and the scanning electron microscope showed that the surface of the D-PP/PP membrane was covered by a cross-linked micro-nano microsphere. The mechanical properties showed that the maximum tensile force of the D-PP/PP composite membrane was 2.34 N, which was 19.4% higher than that of PVDF-PVC (1.96 N). Nano-graphite was added to the coating layer in the experiment. The prepared double-layer PVDF-PVC-nano-graphite/PVDF-PVC (D-PPG/PP) composite membrane reached 153.7 ± 0.5°, the contact angle increasing by 3.3°. The SEM comparison showed that the D-PPG/PP composite membrane had a more obvious micro-nano level microsphere layer. The mechanical properties are also superior. By preparing the D-PP/PP membrane, the mechanical properties of the membrane were improved, and the super-hydrophobic property of the coating was also obtained. At the same time, it was found that adding nano-graphite to the coating layer can better improve the hydrophobic, mechanical, and self-cleaning properties of the D-PP/PP composite membrane.

Dbh+ catecholaminergic cardiomyocytes contribute to the structure and function of the cardiac conduction system in murine heart.

The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.

Cascade dams altered taxonomic and functional composition of bacterioplankton community at the regional scale.

Dams are increasingly disrupting natural river systems, yet studies investigating their impact on microbial communities at regional scale are limited. Given the indispensable role of bacterioplankton in aquatic ecosystems, 16S rRNA gene sequencing was performed to explore how these communities respond to dam-influenced environmental changes at the regional scale in the Shaying River Basin. Our findings revealed that cascade dams create distinct environments, shaping bacterioplankton communities near the dams differently from those in natural rivers. In the upstream of the cascade dams, water quality was superior, while bacterioplankton community structure was simple with weak community interactions. In the midstream, nutrient and heavy metal content were increased, making bacterioplankton structures more susceptible to environmental changes. In the downstream of the cascade dams, water quality had a significant impact on the community and the bacterioplankton structures were highly complex. Additionally, environmental variables significantly influenced bacterioplankton functional groups. However, the response to these factors, as well as the interplay between functional and taxonomic diversity, varied markedly depending on the specific region of the cascade dams. We here delved into the effects of cascade dams on the taxonomic diversity and functional groups of bacterioplankton to provide a theoretical basis for segmentally regulating these dams.

Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice.

Engineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca2+ oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient's own induced pluripotent stem cells.