The Role of the Sensory Input Intervention in Recovery of the Motor Function in Hypoxic Ischemic Encephalopathy Rat Model.

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, Environmental Enrichment (EE) is strictly considered a form of sensory intervention. However, limited research employs EE as a single sensory input intervention to validate outcomes post-intervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions use in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as a neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. Additionally, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared to the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.

Choosing the optimal target area for repeated transcranial magnetic stimulation in treating neuropathic pain in spinal cord injury patients: a comparative analysis.

Objective: The specific target area of repeated transcranial magnetic stimulation (rTMS) in treating neuropathic pain resulting from spinal cord injury (SCI-NP) remains uncertain. Methods: Thirty-four participants with SCI-NP were allocated into three groups, namely, the motor cortex (M1, A) group, the left dorsolateral prefrontal cortex (LDLPFC, B) group, and the control (sham stimulation, C) group. The intervention was administered totally 10 times. Outcome measures assessed pre-(T0) and post-(T1)intervention, including Numerical Rating scale (NRS), anxiety (SAS), depression (SDS), sleep quality (PSQI), brief pain inventory (BPI), and impression of change. Results: All outcomes in groups A and B significantly changed after intervention (p < 0.05), and the delta value (T1-T0) also significantly changed than group C (p < 0.05). The delta value of SDS in the group B was better than the group A, and the change of pain degree in the group B was moderately correlated with the change in PSQI (r = 0.575, p < 0.05). Both patients in the groups A and B showed significant impression of change about their received therapy (p < 0.05). Conclusion: Both targets are effective, but LDLPFC is more effective in reducing depression in SCI-NP. Healthcare providers might select the suitable area according to the specific attributes of their patients.

The role of payment sources in the continuation of rehabilitation therapy in tertiary hospitals for patients with traumatic spinal cord injury: a study in Southwest China.

Medical security support for rehabilitation therapy in China is different from that in other countries. We investigated whether the discharge plan to continue rehabilitation therapy in tertiary hospitals for patients after traumatic spinal cord injury (TSCI) was influenced by payment sources or other conditions. This was a cross-sectional, observational study. Information was collected on the general condition, caregiver, types of payment sources for continued rehabilitation, American Spinal Injury Association Impairment Scale (AIS) scores, and discharge plans. In total, 135 patients with TSCI (107 male, mean age 41.00 ± 13.73 years, mean spinal cord injury duration 238.43 ± 345.54 days) were enrolled. Medical insurance (43%) and out-of-pocket payments (27.4%) were the primary payment sources. Although most patients were beyond the acute phase, 40% continued rehabilitation therapy at other tertiary hospitals. The caregiver, payment sources, injury level, AIS level, and complete urinary tract infection (UTI) were different due to discharge plans (p > .05). Patients seemingly consider a higher AIS level and co-UTI as the requirement for tertiary hospital therapy. In non-medical insurance payment source patients, the discharge plan also differed due to the AIS level and co-UTI (p > .05). However, in medical insurance patients, the discharge plan differed only in terms of TSCI duration (p > .05). The restricted duration of medical coverage restricted the continuation of rehabilitation therapy and influenced the discharge plan of most patients with TSCI.

Cognitive and emotional impairment in stroke survivors: insights from a multi-center study on inpatient rehabilitation therapy.

BACKGROUND: Individuals recovering from stroke often experience cognitive and emotional impairments, but rehab programs tend to focus on motor skills. The aim of this investigation is to systematically assess the change of magnitude of cognitive and emotional function subsequent to a conventional rehabilitative protocol administered to stroke survivors within a defined locale in China. METHODS: This is a multicenter study; a total of 1884 stroke survivors who received in-hospital rehabilitation therapy were assessed on admission (T0) and discharge (T1). The tool of InterRAI was used to assess cognitive, emotional, and behavioral abnormality. RESULTS: The patients aged >60 years, with a history of hypertension, and long stroke onset duration were more exposed to functional impairment (all p < 0.05). Both cognitive and emotional sections were significantly improved at T1 compared to T0 (p < 0.001). Initially, 64.97% and 46.55% of patients had cognitive or emotional impairment at T0, respectively; this percentage was 58.55% and 37.15% at T1. CONCLUSION: Many stroke survivors have ongoing cognitive and emotional problems that require attention. It is essential to focus on rehabilitating these areas during the hospital stay, especially for older patients, those with a longer recovery, and those with hypertension history.

Observation on efficacy and underlying mechanism of cheek acupuncture on ovulation induction for infertile women with PCOS: Case series.

RATIONALE: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth rate compared to clomiphene citrate, although challenges persist in terms of longer stimulation cycles, multiple pregnancies, and the risk of ovarian hyperstimulation syndrome (OHSS). Clinical reports indicate that acupuncture therapy shows promising efficacy in treating patients with PCOS-related infertility, despite a partially unclear understanding of its underlying mechanisms. PATIENT CONCERNS: In this study, one patient did not achieve pregnancy despite more than a year of ovulation induction using clomiphene citrate and letrozole. However, after 3 months of receiving cheek acupuncture therapy, she successfully conceived and gave birth to a liveborn baby. Another patient achieved natural conception and live birth after 2 months of exclusive cheek acupuncture therapy. DIAGNOSIS: PCOS. INTERVENTIONS: Cheek acupuncture therapy. OUTCOMES: Both of them successfully conceived and gave birth to a liveborn baby. LESSONS: These findings suggest that cheek acupuncture therapy can effectively stimulate follicle development and ovulation, potentially improving endometrial receptivity. According to holographic theory, there is a biologically holographic model within the cheek region that shares a homology with the human body structure. This model provides an explanation for the regulatory effects of cheek acupuncture point stimulation on the Hypothalamic-Pituitary-Ovarian axis (HPO), which subsequently influences follicle development and ovulation in patients. Consequently, when cheek acupuncture therapy is applied alone or in combination with ovulation induction medication, patients have the ability to achieve successful pregnancy and experience a smooth delivery.

An in silico scheme for optimizing the enzymatic acquisition of natural biologically active peptides based on machine learning and virtual digestion.

BACKGROUND: As a potential natural active substance, natural biologically active peptides (NBAPs) are recently attracting increasing attention. The traditional proteolysis methods of obtaining effective NBAPs are considerably vexing, especially since multiple proteases can be used, which blocks the exploration of available NBAPs. Although the development of virtual digesting brings some degree of convenience, the activity of the obtained peptides remains unclear, which would still not allow efficient access to the NBAPs. It is necessary to develop an efficient and accurate strategy for acquiring NBAPs. RESULTS: A new in silico scheme named SSA-LSTM-VD, which combines a sparrow search algorithm-long short-term memory (SSA-LSTM) deep learning and virtually digested, was presented to optimize the proteolysis acquisition of NBAPs. Therein, SSA-LSTM reached the highest Efficiency value reached 98.00 % compared to traditional machine learning algorithms, and basic LSTM algorithm. SSA-LSTM was trained to predict the activity of peptides in the proteins virtually digested results, obtain the percentage of target active peptide, and select the appropriate protease for the actual experiment. As an application, SSA-LSTM was employed to predict the percentage of neuroprotective peptides in the virtual digested result of walnut protein, and trypsin was ultimately found to possess the highest value (85.29 %). The walnut protein was digested by trypsin (WPTrH) and the peptide sequence obtained was analyzed closely matches the theoretical neuroprotective peptide. More importantly, the neuroprotective effects of WPTrH had been demonstrated in nerve damage mouse models. SIGNIFICANCE: The proposed SSA-LSTM-VD in this paper makes the acquisition of NBAPs efficient and accurate. The approach combines deep learning and virtually digested skillfully. Utilizing the SSA-LSTM-VD based strategy holds promise for discovering and developing peptides with neuroprotective properties or other desired biological activities.

Effects of an Akt-activating peptide obtained from walnut protein degradation on the prevention of memory impairment in mice.

Akt acts as a central protein influencing multiple pathologies in neurodegenerative diseases including AD and PD, and using Akt activators is a promising management strategy. The current study characterized the effects of an Akt-activating peptide (Glu-Pro-Glu-Val-Leu-Pro, EPEVLR) obtained from walnut protein degradation on D-gal-induced memory impairment in mice. EPEVLR was obtained by hydrolysis of walnut proteins, identification of peptide sequences, and screening for molecular docking sequentially. The MWM test in mice indicated that the oral administration of EPEVLR (80, 200 and 400 mg per kg per day) significantly (p < 0.05) reversed D-gal-induced memory impairment. WB tests of the mouse hippocampus confirmed that EPEVLR could activate Akt by promoting its phosphorylation. In addition, further characterization (including TEM, ELISA, and immunohistochemistry) related to Akt phosphorylation showed lower Aß and p-tau levels, as well as more autophagosomes than those in the model group. Moreover, the EPEVLR treatment significantly increased Lactobacillus abundance and reduced Helicobacter abundance in the gut microbiome and caused up-regulation of SCFAs and down-regulation of LPS of serum metabolites. Therefore, EPEVLR ingestion reversed cognitive impairment symptoms, possibly related to the activation of Akt and regulation of the intestinal flora pathway. Consumption of an EPEVLR-containing diet is beneficial for treating cognitive dysfunction.

Pharmacological profiling of a berbamine derivative for lymphoma treatment.

ABSTRACT: Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) has been identified as a potential target for treating cancer. Based on our previous study of berbamine (BBM) as a CAMKIIγ inhibitor, we have synthesized a new BBM derivative termed PA4. Compared with BBM, PA4 showed improved potency and specificity and was more cytotoxic against lymphoma and leukemia than against other types of cancer. In addition to indirectly targeting c-Myc protein stability, we demonstrated that its cytotoxic effects were also mediated via increased reactive oxygen species production in lymphoma cells. PA4 significantly impeded tumor growth in vivo in a xenograft T-cell lymphoma mouse model. Pharmacokinetics studies demonstrated quick absorption into plasma after oral administration, with a maximum concentration of 1680 ± 479 ng/mL at 5.33 ± 2.31 hours. The calculated oral absolute bioavailability was 34.1%. Toxicity assessment of PA4 showed that the therapeutic window used in our experiments was safe for future development. Given its efficacy, safety, and favorable pharmacokinetic profile, PA4 is a potential lead candidate for treating lymphoma.

Treatment of lactational mastitis with Gualou Xiaoyong soup and painless lactation promoting technique: A case series.

BACKGROUND: Lactational mastitis is a common and frequently disease in clinical practice, characterized by acute inflammation of the mammary ducts and surrounding connective tissues. The main manifestations are damage to the mammary gland acini, edema, and invasion of inflammatory cells. If not treated properly, it may lead to the formation of breast abscesses, or even sepsis, septic shock, and chronic inflammation of the breast, which may cause the disease to persist or recur multiple times, so that the patients suffer extreme pain, and the health of both the mother and child are directly affected. This disease not only causes suffering for women but also may result in the cessation of breastfeeding. Therefore, rapid and effective treatment is particularly important. CASE SUMMARY: We report 3 cases of lactation mastitis patients showing good clinical efficacy after being treated with the Chinese medicine Gualou Xiaoyong soup and painless lactation promoting techniques. Gualou Xiaoyong soup combined with painless lactation promotion techniques can significantly reduce and eliminate the clinical symptoms of patients in the short term, and rapidly restore inflammatory indicators such as total white blood cells, neutrophils, C-reactive protein, and procalcitonin to normal levels. The patchy low echo area of the breast under B-ultrasound also disappears quickly. Therefore, we believe that this method is a good way to treat lactational mastitis and is worthy of clinical reference and research. However, this study has certain limitations: this study lacks a large sample of prospective controlled studies. Next, we will continue to collect relevant cases and conduct prospective case randomized controlled clinical studies. CONCLUSION: The treatment of lactation mastitis with Gualou Xiaoyong soup and painless lactation promoting techniques can achieve good clinical results.

Sanji Peiyuan decoction combined with dydrogesterone in the treatment of massive subchorionic hematoma: A case report.

RATIONALE: Subchorionic Hematoma, often referred to as Bruce hematoma, can lead to serious obstetric complications such as intrauterine growth restriction and fetal death, as well as early and late pregnancy miscarriage, placental abruption, and premature rupture of membranes, posing great harm to both mother and fetus. PATIENT CONCERNS: At present, Western medical treatments have not shown satisfactory results, necessitating the discovery of more effective clinical treatment methods. DIAGNOSES: Threatened miscarriage, Subchorionic hematoma, Iron deficiency anemia (mild). INTERVENTIONS: Sanji Peiyuan decoction combined with dydrogesterone. OUTCOMES: Following 17 days of treatment with Sanji Peiyuan decoction and oral dydrogesterone tablets, the hematoma was no longer detectable by ultrasound. The patient experienced no symptoms such as abdominal pain, bloating, or vaginal bleeding. She successfully gave birth around her due date, with both the mother and child in good health. LESSONS: The combination of Sanji Peiyuan decoction and oral dydrogesterone tablets shows promising clinical efficacy in treating Massive Subchorionic Hematomas. This method merits further clinical research.

CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.

BACKGROUND AND AIMS: Although the benefits of vertical sleeve gastrectomy (VSG) surgery are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine the role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG. APPROACH AND RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, short hairpin RNA-mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12α-OH/non-12α-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation from wild type-VSG mice (vs. fecal microbiota transplantation from wild-type-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received fecal microbiota transplantation from knockout-sham and knockout-VSG mice. CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and gut microbiota profile by targeting CYP8B1 may provide novel insight into the development of therapies that noninvasively mimic bariatric surgery to treat obesity and its complications.

Current status of rehabilitation services and problems in Yunnan Province, Southwest China: a general doctors' questionnaire-based study.

OBJECTIVES: Community-based hospitals in China lack physicians, especially rehabilitation physicians. Recently, several financial resources have been developed to prepare general doctors for community-based hospitals. These doctors seem to be the best choices for assuming the role of a rehabilitation physician. However, their willingness and in-depth information from their perspectives have not been previously investigated. MATERIALS AND METHODS: We conducted a general investigation of rehabilitation resources in Yunnan, a province located in Southwest China with a population of more than 40 million. Our investigation covered the entire Yunnan Province from December 2020 to May 2022. The questionnaire was administered to 670 general doctors in 112 community hospitals randomly selected in Yunnan Province based on their willingness to assume the role of rehabilitation physicians and obstructive factors to process the rehabilitation services. The reliability and validity of the questionnaire were evaluated, and items regarding their general condition were analyzed. RESULTS: Cronbach's alpha and Kaiser-Meyer-Olkin values were 0.748 and 0.729, respectively. The measure comprises four factors: common disease, demand for training to improve skills, subjective/objective factors, and proactivity to recommend rehabilitation therapy. More than 20% of general doctors were unwilling to take on the role of rehabilitation physicians, and their willingness was related to satisfaction with their current job, comprehension of community-based rehabilitation, and comprehension of government support (p < .05). CONCLUSIONS: From the perspective of general doctors, the reimbursement rate for medical insurance, which burdens patients, is the greatest problem in the process of developing community-based hospital rehabilitation services. Offering professional training to increase their capacity and developing common practices to increase doctors' proactivity to recommend rehabilitation therapy may help increase the future support of medical insurance and increase general doctors' willingness to take on the role of a rehabilitation physician.

SARS-CoV-2 HaploGraph: visualization of SARS-CoV-2 haplotype spread in Japan.

Since the early phase of the coronavirus disease 2019 (COVID-19) pandemic, a number of research institutes have been sequencing and sharing high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes to trace the route of infection in Japan. To provide insight into the spread of COVID-19, we developed a web platform named SARS-CoV-2 HaploGraph to visualize the emergence timing and geographical transmission of SARS-CoV-2 haplotypes. Using data from the GISAID EpiCoV database as of June 4, 2022, we created a haplotype naming system by determining the ancestral haplotype for each epidemic wave and showed prefecture- or region-specific haplotypes in each of four waves in Japan. The SARS-CoV-2 HaploGraph allows for interactive tracking of virus evolution and of geographical prevalence of haplotypes, and aids in developing effective public health control strategies during the global pandemic. The code and the data used for this study are publicly available at: https://github.com/ktym/covid19/.

Rate-dependent stress-order coupling in main-chain liquid crystal elastomers.

Liquid crystal elastomers (LCEs) exhibit significant viscoelasticity. Although the rate-dependent stress-strain relation of LCEs has already been widely observed, the effect of the intricate interplay of director rotation and network extension on the viscoelastic behavior of main-chain LCEs remains inadequately understood. In this study, we report real-time measurements of the stress, director rotation, and all strain components in main-chain nematic LCEs subjected to uniaxial tension both parallel and tilted to the initial directors at different loading rates and relaxation tests. We find that both network extension and director rotation play roles in viscoelasticity, and the characteristic relaxation time of the network extension is much larger than that of the director rotation. Interestingly, the gradual change of the director in a long-time relaxation indicates the director reorientation delay is not solely due to the viscous rotation of liquid crystals but also arises from its coupling with the highly viscous network. Additionally, significant rate-dependent shear strain occurs in LCEs under uniaxial tension, showing non-monotonic changes when the angle between the stretching and the initial director is large enough. Finally, a viscoelastic constitutive model, only considering the viscosity of the network by introducing multiplicative decomposition of the deformation gradient, is utilized to manifest the relation between rate-dependent macroscopic deformation and microscopic director rotation in LCEs.

Clinical efficacy of Gualou Xiaoyong Decoction and painless lactation manipulation in treating lactation acute mastitis and breast abscess: An observational study.

Information on the effects of Chinese medicine in the treatment of lactational acute mastitis and breast abscess is limited; thus, we conducted an observational study to analyze the clinical efficacy of Gualou Xiaoyong Decoction combined with painless lactation manipulation in the treatment of lactational acute mastitis and breast abscess. A total of 41 patients with lactational acute mastitis and breast abscess who were treated with Gualou Xiaoyong Decoction and painless lactation manipulation from October 2021 to October 2022 were included in this study. The age, fetal times(primiparous/multiparous), delivery mode (cesarean section/vaginal delivery), onset time, breast lump diameter, skin rash diameter, body temperature, visual analogue score, blood routine, C-reactive protein, procalcitonin, bacterial culture in milk, B ultrasound and other data of these patients were statistically analyzed. After treatment, the breast lump diameter of these patients decreased significantly, the skin rash diameter was reduced or disappeared, the body temperature decreased or returned to a normal range, and the visual analogue score also decreased. Besides, these patients had a decreased total number of white blood cells and a reduced percentage of neutrophils, C-reactive protein, and procalcitonin after treatment. In addition, bacteria in the milk of most patients disappeared, and there was no abnormality in B ultrasonic imaging. Except for 2 patients with breast abscess who stopped breastfeeding on the affected side for 1 day and 3 days respectively, all other patients continued to provide breast milk for their infants, and no adverse reactions were observed in these infants. The combination of Gualou Xiaoyong Decoction and painless lactation manipulation can achieve favorable clinical effects in the treatment of lactational acute mastitis and breast abscess. This combined therapy has good efficacy, short course of treatment, low costs, and great convenience with the avoidance of pain, hospitalization, influence on lactation, breast scar and other adverse outcomes.

Multi-dimensional deep learning drives efficient discovery of novel neuroprotective peptides from walnut protein isolates.

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are multi-factor induced neurological disorders that require management from multiple pathologies. The peptides from natural proteins with diverse physiological activity can be candidates as multifunctional neuroprotective agents. However, traditional methods for screening neuroprotective peptides are not only time-consuming and laborious but also poorly accurate, which makes it difficult to effectively obtain the needed peptides. In this case, a multi-dimensional deep learning model called MiCNN-LSTM was proposed to screen for multifunctional neuroprotective peptides. Compared to other multi-dimensional algorithms, MiCNN-LSTM reached a higher accuracy value of 0.850. The MiCNN-LSTM was used to acquire candidate peptides from walnut protein hydrolysis. Following molecular docking, behavioral and biochemical index experimental validation eventually found 4 hexapeptides (EYVTLK, VFPTER, EPEVLR and ELEWER) demonstrating excellent multifunctional neuroprotective properties. Therein, EPEVLR performed the best and can be investigated in depth as a multifunctional neuroprotective agent. This strategy will greatly improve the efficiency of screening multifunctional bioactive peptides, and it will be beneficial for the development of food functional peptides.

Gell: A GPU-powered 3D hybrid simulator for large-scale multicellular system.

As a powerful but computationally intensive method, hybrid computational models study the dynamics of multicellular systems by evolving discrete cells in reacting and diffusing extracellular microenvironments. As the scale and complexity of studied biological systems continuously increase, the exploding computational cost starts to limit large-scale cell-based simulations. To facilitate the large-scale hybrid computational simulation and make it feasible on easily accessible computational devices, we develop Gell (GPU Cell), a fast and memory-efficient open-source GPU-based hybrid computational modeling platform for large-scale system modeling. We fully parallelize the simulations on GPU for high computational efficiency and propose a novel voxel sorting method to further accelerate the modeling of massive cell-cell mechanical interaction with negligible additional memory footprint. As a result, Gell efficiently handles simulations involving tens of millions of cells on a personal computer. We compare the performance of Gell with a state-of-the-art paralleled CPU-based simulator on a hanging droplet spheroid growth task and further demonstrate Gell with a ductal carcinoma in situ (DCIS) simulation. Gell affords ~150X acceleration over the paralleled CPU method with one-tenth of the memory requirement.

Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases.

The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of pathological molecules and microorganisms. Bile acids are small molecules synthesized from cholesterol in the liver, secreted into the duodenum, and transformed to secondary or tertiary bile acids by the gut microbiota. Bile acids interact with bile acid receptors (BARs) or gut microbiota, which plays a key role in maintaining the homeostasis of the intestinal barrier. In this review, we summarize and discuss the recent studies on bile acid disorder associated with intestinal barrier dysfunction and related diseases. We focus on the roles of bile acids, BARs, and gut microbiota in triggering intestinal barrier dysfunction. Insights for the future prevention and treatment of intestinal barrier dysfunction and related diseases are provided.

Achieving tissue-level softness on stretchable electronics through a generalizable soft interlayer design.

Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young's moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa-over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices.

High-throughput printing of combinatorial materials from aerosols.

The development of new materials and their compositional and microstructural optimization are essential in regard to next-generation technologies such as clean energy and environmental sustainability. However, materials discovery and optimization have been a frustratingly slow process. The Edisonian trial-and-error process is time consuming and resource inefficient, particularly when contrasted with vast materials design spaces1. Whereas traditional combinatorial deposition methods can generate material libraries2,3, these suffer from limited material options and inability to leverage major breakthroughs in nanomaterial synthesis. Here we report a high-throughput combinatorial printing method capable of fabricating materials with compositional gradients at microscale spatial resolution. In situ mixing and printing in the aerosol phase allows instantaneous tuning of the mixing ratio of a broad range of materials on the fly, which is an important feature unobtainable in conventional multimaterials printing using feedstocks in liquid-liquid or solid-solid phases4-6. We demonstrate a variety of high-throughput printing strategies and applications in combinatorial doping, functional grading and chemical reaction, enabling materials exploration of doped chalcogenides and compositionally graded materials with gradient properties. The ability to combine the top-down design freedom of additive manufacturing with bottom-up control over local material compositions promises the development of compositionally complex materials inaccessible via conventional manufacturing approaches.