Tree-Based Reinforcement Learning for Identifying Optimal Personalized Treatment Decisions for Hand Deformity in Rheumatoid Arthritis.

BACKGROUND: Silicone metacarpophalangeal joint arthroplasty (SMPA) can reconstruct metacarpophalangeal (MCP) joint deformities in the rheumatoid hand, but patient selection criteria for the procedure remains unclear. We used statistical learning to elucidate patient selection criteria that will enhance long-term patient-reported and functional outcomes in patients with severe hand rheumatoid arthritis (RA). METHODS: This is a secondary analysis of a prospective study of 169 adults with severe hand RA (average combined ulnar deviation (UD) and extensor lag (EL) at the MCP joint ≥ 50 degrees, per finger) with one-year follow-up, conducted at three centers in the United States and England from January 1, 2004, to December 31, 2011. Primary outcomes were Michigan Hand Outcomes Questionnaire (MHQ) pain sub-score, changes in EL, UD, and Arthritis Impact Measurement Scale (AIMS2) score. A tree-based reinforcement learning (T-RL) model was used to estimate clinical decision rules for treatment. RESULTS: 132 patients (mean[SD], 61[9] years; 108[72%] female) were included in the SMPA (n=50) and non-SMPA (n=82) cohorts. To minimize EL and UD, patients should undergo SMPA. To minimize pain, patients older than 55 should undergo SMPA. To increase hand-related quality-of-life (QOL), patients with grip strength <12 kg should undergo SMPA. Estimations with imputed missing data were similar, aside from a lower grip strength (<8 kg) threshold for hand-related QOL. CONCLUSION: Unless there is significant comorbidity that precludes surgery, most patients older than 55 with severe hand RA will have improved QOL, pain, and function after SMPA. Patients with preserved grip strength may benefit from continued medical management.

Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo.

Background: Since RNA sequencing has shown that induced pluripotent stem cells (iPSCs) share a common antigen profile with tumor cells, cancer vaccines that focus on iPSCs have made promising progress in recent years. Previously, we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia (T-ALL) have a gene expression profile similar to that of T-ALL cell lines. Methods: Mice with T-ALL were treated with dendritic and T (DC-T) cells loaded with intact and complete antigens from T-ALL-derived iPSCs (T-ALL-iPSCs). We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry, cytokine release assay, acute toxicity experiments, long-term toxicity experiments, and other methods. Results: Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity. Conclusion: T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

The utilization of chitosan/Bletilla striata hydrogels to elevate anti-adhesion, anti-inflammatory and pro-angiogenesis properties of polypropylene mesh in abdominal wall repair.

Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde Bletilla striata polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.

An αIIbß3 Monoclonal Antibody Traps a Semi-Extended Conformation and Allosterically Inhibits Large Ligand Binding.

Monoclonal antibodies (mAbs) have provided valuable information on the structure and function of platelet αIIbß3. Protein disulfide isomerase (PDI) has been implicated in αIIbß3 activation and binds to thrombin-activated αIIbß3. Using human platelets as immunogen, we identified a new mAb (R21D10) that inhibits the binding of PDI to platelets activated with a thrombin receptor-activating peptide (T6). R21D10 also partially inhibits T6-induced fibrinogen and PAC-1 binding to platelets, as well as T6- and ADP-induced platelet aggregation. Mutual competition experiments show that R21D10 does not inhibit binding of mAbs 10E5 (anti-αIIb cap domain) or 7E3 (anti-ß3 ß-I domain) and immunoblot studies indicate that R21D10 binds to ß3. Dissociation of αIIbß3 by EDTA had minimal effect on R21D10 binding. Cryo-electron microscopy of the αIIbß3-R21D10 Fab complex reveals that R21D10 binds to the ß3 I-EGF1 domain and traps an intermediate conformation of αIIbß3 with semi-extended leg domains. Binding of R21D10 produces a major structural change in the ß3 I-EGF2 domain associated with a new interaction between the ß3 I-EGF2 and the αIIb thigh domains, which may prevent the swing-out motion of the ß3 hybrid domain required for high-affinity ligand binding and protect αIIbß3 from EDTA-induced dissociation. R21D10 partially reverses the ligand binding priming effect of eptifibatide, suggesting that it can convert the swung-out conformation into the semi-extended conformation. We conclude that R21D10 inhibits ligand binding to αIIbß3 via a unique allosteric mechanism, which may or may not be related to its inhibition of PDI binding.

Angelica sinensis polysaccharides promote extramedullary stress erythropoiesis via ameliorating splenic glycolysis and EPO/STAT5 signaling-regulated macrophages.

Conventional treatments exhibit various side effects on chronic stress anemia. Extramedullary stress erythropoiesis is a compensatory mechanism, which may effectively counteract anemia. Angelica sinensis polysaccharides (ASP) are the main active ingredient found in Angelica sinensis and exhibit antioxidant and hematopoietic effects. However, the effects of ASP on extramedullary stress erythropoiesis remain to be unclear. Here, we demonstrated the protective effects of ASP on chemotherapeutic drug 5-fluorouracil (5-FU)-induced decline in peripheral blood parameters such as RBC counts, HGB, HCT, and MCH, and the decline of BFU-E colony enumeration in the bone marrow. Meanwhile, ASP promoted extramedullary erythropoiesis, increasing cellular proliferation in the splenic red pulp and cyclin D1 protein expression, abrogating phase G0/G1 arrest of c-kit+ cells in mouse spleen. RT-qPCR and immunohistochemistry further revealed that ASP increased macrophage chemokine Ccl2 genetic expression and the number of F4/80+ macrophages in the spleen. The colony-forming assay showed that ASP significantly increased splenic BFU-E. Furthermore, we found that ASP facilitated glycolytic genes including Hk2, Pgk1, Pkm, Pdk1, and Ldha via PI3K/Akt/HIF2α signaling in the spleen. Subsequently, ASP declined pro-proinflammatory factor IL-1ß, whereas upregulating erythroid proliferation-associated genes Gdf15, Bmp4, Wnt2b, and Wnt8a. Moreover, ASP facilitated EPO/STAT5 signaling in splenic macrophages, thus enhancing erythroid lineage Gata2 genetic expression. Our study indicated that ASP may improve glycolysis, promoting the activity of splenic macrophages, subsequently promoting erythroid progenitor cell expansion. Additionally, ASP facilitates erythroid differentiation via macrophage-mediated EpoR/STAT5 signaling; suggesting it might be a promising strategy for stress anemia treatment.

Construction and validation of a risk prediction model for postoperative ICU admission in patients with colorectal cancer: clinical prediction model study.

BACKGROUND: Transfer to the ICU is common following non-cardiac surgeries, including radical colorectal cancer (CRC) resection. Understanding the judicious utilization of costly ICU medical resources and supportive postoperative care is crucial. This study aimed to construct and validate a nomogram for predicting the need for mandatory ICU admission immediately following radical CRC resection. METHODS: Retrospective analysis was conducted on data from 1003 patients who underwent radical or palliative surgery for CRC at Ningxia Medical University General Hospital from August 2020 to April 2022. Patients were randomly assigned to training and validation cohorts in a 7:3 ratio. Independent predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression in the training cohort to construct the nomogram. An online prediction tool was developed for clinical use. The nomogram's calibration and discriminative performance were assessed in both cohorts, and its clinical utility was evaluated through decision curve analysis (DCA). RESULTS: The final predictive model comprised age (P = 0.003, odds ratio [OR] 3.623, 95% confidence interval [CI] 1.535-8.551); nutritional risk screening 2002 (NRS2002) (P = 0.000, OR 6.129, 95% CI 2.920-12.863); serum albumin (ALB) (P = 0.013, OR 0.921, 95% CI 0.863-0.982); atrial fibrillation (P = 0.000, OR 20.017, 95% CI 4.191-95.609); chronic obstructive pulmonary disease (COPD) (P = 0.009, OR 8.151, 95% CI 1.674-39.676); forced expiratory volume in 1 s / Forced vital capacity (FEV1/FVC) (P = 0.040, OR 0.966, 95% CI 0.935-0.998); and surgical method (P = 0.024, OR 0.425, 95% CI 0.202-0.891). The area under the curve was 0.865, and the consistency index was 0.367. The Hosmer-Lemeshow test indicated excellent model fit (P = 0.367). The calibration curve closely approximated the ideal diagonal line. DCA showed a significant net benefit of the predictive model for postoperative ICU admission. CONCLUSION: Predictors of ICU admission following radical CRC resection include age, preoperative serum albumin level, nutritional risk screening, atrial fibrillation, COPD, FEV1/FVC, and surgical route. The predictive nomogram and online tool support clinical decision-making for postoperative ICU admission in patients undergoing radical CRC surgery. TRIAL REGISTRATION: Despite the retrospective nature of this study, we have proactively registered it with the Chinese Clinical Trial Registry. The registration number is ChiCTR2200062210, and the date of registration is 29/07/2022.

MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway.

Microsomal glutathione transferase 3 (MGST3) regulates eicosanoid and glutathione metabolism. These processes are associated with oxidative stress and apoptosis, suggesting that MGST3 might play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that knockdown (KD) of MGST3 in cell lines reduced the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the resulting amyloidogenesis. Interestingly, MGST3 KD did not alter intracellular ROS level but selectively reduced the expression of apoptosis indicators which could be associated with the receptor of cysteinyl leukotrienes (cysLTs), the downstream metabolites of MGST3 in arachidonic acid pathway. We then showed that the effect of MGST3 on BACE1 was independent of cysLTs but involved a translational mechanism. Further RNA-seq analysis identified that regulator of G-protein signaling 4 (RGS4) was a target gene of MGST3. Silencing of RGS4 inhibited BACE1 translation and prevented MGST3 KD-mediated reduction of BACE1. The potential mechanism was related to AKT activity, as the protein level of phosphorylated AKT (p-AKT) was significantly reduced by silencing of MGST3 and RGS4, and the AKT inhibitor abolished the effect of MGST3/RGS4 on p-AKT and BACE1. Together, MGST3 regulated amyloidogenesis by controlling BACE1 protein expression, which was mediated by RGS4 and downstream AKT signaling pathway.

Scale Invariance of a Spherical Unitary Fermi Gas.

A unitary Fermi gas in an isotropic harmonic trap is predicted to show scale and conformal symmetry that have important consequences in its thermodynamic and dynamical properties. By experimentally realizing a unitary Fermi gas in an isotropic harmonic trap, we demonstrate its universal expansion dynamics along each direction and at different temperatures. We show that as a consequence of SO(2,1) symmetry, the measured release energy is equal to that of the trapping energy. We further observe the breathing mode with an oscillation frequency twice the trapping frequency and a small damping rate, providing the evidence of SO(2,1) symmetry. In addition, away from resonance when scale invariance is broken, we determine the effective exponent γ that relates the chemical potential and average density along the BEC-BCS crossover, which qualitatively agrees with the mean field predictions. This Letter opens the possibility of studying nonequilibrium dynamics in a conformal invariant system in the future.

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.

ARID1A is involved in DNA double-strand break repair in gastric cancer.

Background: Defects in DNA damage repair can cause genetic mutations, which in turn can cause different types of cancers. Chromatin remodeling complexes, which help repair damaged DNA, can cause the chromatin structure to change as a result of DNA damage. ARID1A may play a role in the process of DNA damage repair, and arid1a may be related to the occurrence and development of gastric cancer (GC). This study aimed to investigate the mechanism of ARID1A regulating the DNA damage repair of gastric adenocarcinoma cell lines AGS and SGC-7901 and its effect on migration, proliferation and apoptosis. Methods: The expression of ARID1A plasmid was detected by Western blot and real-time polymerase chain reaction (PCR). The effect of etoposide (ETO) on the survival rate of AGS and SGC-7901 gastric adenocarcinoma cell lines was detected by MTT assay. The DNA double-strand break model was established by ETO and then passed through the comet assay and immunofluorescence co-localization to observe DNA damage; western blot method was used to detect the effect of ARID1A on the expression of related proteins in DNA damage repair pathway in gastric adenocarcinoma cells; scratch test and colony formation experiments were used to observe ARID1A migration and proliferation of gastric adenocarcinoma cells. The flow cytometry was used to detect the effect of ARID1A on apoptosis of gastric adenocarcinoma cells. Results: The expression of mRNA and protein was increased after transfection of ARID1A plasmid. ETO was confirmed by MTT assay to inhibit cell survival in a dose-dependent manner. After the DNA double-strand break model was established by ETO, the expression levels of phospho-ataxia telangiectasia mutated (p-ATM) protein increased in the overexpressed ARID1A group. Meanwhile, the overexpressed ARID1A group had a shortened tail moment, and γ-H2AX and ARID1A co-localized in the DNA damage site of the nucleus. The over-expressed ARID1A group had weaker wound healing ability, reduced number of clone formation, and increased apoptosis rate. Conclusions: ARID1A may repair DNA double-strand breaks caused by ETO by p-ATM pathway; ARID1A can inhibit the migration and proliferation of gastric adenocarcinoma cells and promote apoptosis. Our findings indicate that ARID1A could serve as a therapeutic target and biomarker for GC patients.

Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data.

BACKGROUND: Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. METHODS: Utilizing patient data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. RESULTS: The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. CONCLUSIONS: The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

MBNL2 promotes aging-related cardiac fibrosis via inhibited SUMOylation of Krüppel-like factor4.

Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-ß1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-ß1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

Hepatic amyloidosis in a patient with chronic liver failure: A case report.

BACKGROUND: Amyloidosis is a rare disorder that can be classified into various types, and the most common type is the systemic light chain type. The prognosis of this disease is extremely poor. In general, amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells. Cases in which the liver is the primary organ affected by amyloidosis, as in this report, are less common in clinical practice. CASE SUMMARY: A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes. His condition persisted, and he developed chronic liver failure, with severe cholestasis in the later stage that was gradually accompanied by renal injury. Ultimately, he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination. CONCLUSION: Hepatic amyloidosis rarely occurs in the clinic, and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.

Real-Time Study of the Specific Interactions of Lactoferrin with Mimicked Heparan Sulfate Meshes Using Ordered Porous Layer Interferometry.

Heparan sulfate (HS) meshes within the glycocalyx on cell surfaces have protein recognition ability and have been crucial for gaining insights into vital bioprocesses, such as viral infection, cancer development, and inflammation. The protein recognition ability is determined by the mesh property and compositions of HS, although little attention has been paid to the effect of the mesh property on the recognition. An in-depth specificity study of protein-HS-mesh recognition is essential to illustrate related biological functions. Here, ordered porous layer interferometry is applied to study the interaction behavior between mimicked HS meshes and lactoferrin (LF). Our work aimed at mimicking HS meshes with heparin, a widely used substitute of HS, and analyzing the specific LF-heparin-mesh interaction mechanism by inhibiting the nonspecific interaction in a blended sample. We found that the counterion release-based electrostatic interaction is dominant in the specific LF-heparin-mesh recognition. Furthermore, we detail the contributions of nonspecific and specific interactions to the recognition. We illustrate that the concentrated charge distribution of the proteins appears to be primarily related to this robust, specific recognition.

HMGB1/TLR4 axis promotes pyroptosis after ICH by activating the NLRP3 inflammasome.

BACKGROUND: We previously reported that the HMGB1/TLR4 axis promoted inflammation during the acute phase of intracerebral hemorrhage. Given that this phase is known to involve neuronal pyroptosis and neuroinflammation, here we explore whether HMGB1/TLR signaling activate inflammasome and pyroptosis after intracerebral hemorrhage. METHODS: Autologous blood was injected into Sprague-Dawley rats to induce intracerebral hemorrhage. Neurological deficits were assessed using a modified neurological severity score. These expression and localization of NLRP1 and NLRP3 inflammasomes, as well as the levels of pyroptosis and pyroptosis-associated proteins were assessed using Western blot or immunocytochemistry. These experiments were repeated in animals that received treatment with short interfering RNAs against NLRP1 or NLRP3, with HMGB1 inhibitor ethyl pyruvate or TLR4 inhibitor TAK-242. RESULTS: Intracerebral hemorrhage upregulated NLRP1 and NLRP3 in the ipsilateral striatum and increased the proportions of these cells that were pyroptosis-positive. Additionally, the levels of caspase protein family (e.g., pro-caspase-1 and caspase-1), apoptosis-associated speck-like protein (ASC), pro-interleukin-1ß (IL-1ß), and IL-1ß were also elevated. These effects on pyroptosis and associated neurological deficit, were partially reversed by knockdown of NLRP1 or NLRP3, or by inhibition of HMGB1 or TLR4. Inhibition of HMGB1 or TLR4 resulted in the downregulation NLRP3 but not NLRP1. CONCLUSIONS: The HMGB1/TLR4 signaling may activate the NLRP3 inflammasome during the acute phase of intracerebral hemorrhage, resulting in the inflammatory process known as pyroptosis. These insights suggest potential therapeutic targets for the mitigation tissue injury and associated neurological deficits following hemorrhagic stroke.

M2 macrophages promote PD-L1 expression in triple-negative breast cancer via secreting CXCL1.

BACKGROUND: M2 macrophages are known to play a significant role in the progression of triple-negative breast cancer (TNBC) by creating an immunosuppressive microenvironment. The aim of this study is to investigate the impact of M2 macrophages on TNBC and their correlation with programmed death-ligand 1 (PD-L1) expression. METHODS: We employed a co-culture system to analyze the role of the mutual regulation of M2 macrophages and TNBC cells. Employing a multifaceted approach, including bioinformatics analysis, Western blotting, flow cytometry analysis, ELISA, qRT-PCR, lentivirus infection, mouse models, and IHC, we aimed to elucidate the influence and mechanism of M2 macrophages on PD-L1 expression. RESULTS: The results showed a substantial infiltration of M2 macrophages in TNBC tissue, which demonstrated a positive correlation with PD-L1 expression. CXCL1 exhibited abnormally high expression in M2 macrophages and enhanced the expression of PD-L1 in TNBC cells. Notably, silencing CXCL1 or its receptor CXCR2 inhibited M2 macrophages-induced expression of PD-L1. Mechanistically, CXCL1 derived from M2 macrophages binding to CXCR2 activated the PI3K/AKT/NF-κB signaling pathway, resulting in increased PD-L1 expression in TNBC. CONCLUSION: Broadly speaking, these results provide evidence for the immunosuppressive role of M2 macrophages and CXCL1 in TNBC cells, indicating their potential as therapeutic biomarkers.

Tissue microenvironment induces tissue specificity of ILC2.

Type 2 innate lymphoid cells were found to be members of the innate immune cell family, which is involved in innate and adaptive immunity to resist the invasion of foreign antigens and induce allergic reactions caused by allergens. The advancement of ILC2 research has pointed out that ILC2s have a high degree of diversity, challenging the notion of their homogeneity as a cellular population. An increasing number of studies indicate that ILC2 is a cell population with tissue specificity which can be induced by the tissue microenvironment. In addition, crosstalk between tissues can change ILC2 functions of migration and activation. Here, we emphasize that ILC2 undergoes adaptive changes under the regulation of the tissue microenvironment and distant tissues, thereby coordinating the organization's operation. In addition, ILC2 alterations induced by the tissue microenvironment are not limited to the ILC2 cell population, and ILC2 can also transdifferentiate into another class of ILC cell population (ILC1 or ILC3). In this review, we summarized the tissue-specific effects of ILC2 by tissue microenvironment and focused on the function of ILC2 in inter-tissue crosstalk. Lastly, we discussed the transdifferentiations of ILC2 caused by the abnormal change in tissue environment.

Three-dimensional pore structure of the decellularized parsley scaffold regulates myogenic differentiation for cell cultured meat.

Decellularized plant scaffolds have been used to develop edible scaffolds for cell cultured meat because of their natural structures similar to that of mammalian tissues. However, their diverse three-dimensional (3D) porous structures may lead to differences in myogenic differentiation of skeletal muscle cells. In this study, parsley plant tissues were decellularized and modified by type A gelatin and transglutaminase while retaining, respectively, longitudinal fibrous and transverse honeycomb pore structures. The effects of the structure of the decellularized parsley scaffold on the proliferation and myogenic differentiation of C2C12 cells were investigated and the quality of cell cultured meat was evaluated. The results showed that fibrous pore structure guided cells to be arranged in parallel, whereas honeycomb pore structure connected cells in a circular pattern. After induced differentiation, the fibrous scaffolds were more inclined to form multinucleated myotubes with higher expression of myogenic genes and proteins, and the final cell-based meat contained higher total protein content. Decellularized plant scaffolds with fibrous pore structure were more suitable for myogenic differentiation of C2C12 cells, providing support to the development of edible scaffolds for cultured meat. PRACTICAL APPLICATION: This study investigated the different three-dimensional (3D) pore structure of parsley parenchyma to gain insight into how the 3D pore structure of decellularized plant scaffolds regulates myogenic differentiation, which is expected to address the unstable myogenic differentiation of skeletal muscle cells on decellularized plant scaffolds in cell culture meat production.

Fluorogenic Rhodamine-Based Chemigenetic Biosensor for Monitoring Cellular NADPH Dynamics.

Ratiometric biosensors employing Förster Resonance Energy Transfer (FRET) enable the real-time tracking of metabolite dynamics. Here, we introduce an approach for generating a FRET-based biosensor in which changes in apparent FRET efficiency rely on the analyte-controlled fluorogenicity of a rhodamine rather than the commonly used distance change between donor-acceptor fluorophores. Our fluorogenic, rhodamine-based, chemigenetic biosensor (FOCS) relies on a synthetic, protein-tethered FRET probe, in which the rhodamine acting as the FRET acceptor switches in an analyte-dependent manner from a dark to a fluorescent state. This allows ratiometric sensing of the analyte concentration. We use this approach to generate a chemigenetic biosensor for nicotinamide adenine dinucleotide phosphate (NADPH). FOCS-NADPH exhibits a rapid and reversible response toward NAPDH with a good dynamic range, selectivity, and pH insensitivity. FOCS-NADPH allows real-time monitoring of cytosolic NADPH fluctuations in live cells during oxidative stress or after drug exposure. We furthermore used FOCS-NADPH to investigate NADPH homeostasis regulation through the pentose phosphate pathway of glucose metabolism. FOCS-NADPH is a powerful tool for studying NADPH metabolism and serves as a blueprint for the development of future fluorescent biosensors.

A Highly Responsive Graphene Oxide Humidity Sensor Based on PVA Nanofibers.

Graphene oxide (GO) humidity sensors based on poly(vinyl alcohol) (PVA) nanofibers have been proposed. The PVA nanofiber layers of different densities were obtained by adjusting the electrospinning time. Then, GO films were deposited on PVA nanofibers by a spin-coating method. The electrical properties of GO films are improved due to the increased distribution of PVA nanofibers in the GO films. The humidity sensors exhibit good sensitivity under a high relative humidity range of 40-80%. The response of sensors has reached 98.44% at a humidity level of 80% RH. The GO/PVA sensors have good stability at various humidity levels for 1 week. Furthermore, the GO/PVA sensors were used for respiration monitoring under different statuses. These sensors have good application prospects in the respiratory detection and analysis of diseases.