Long-term swimming exercise attenuates right ventricular hypertrophy via modulating meta-inflammation in monocrotaline-induced pulmonary hypertensive rats.

Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary vascular resistance, resulting in right ventricular (RV) hypertrophy and, eventually, failure, which remains the primary cause of mortality in PAH patients. While current PAH therapies primarily target vascular abnormalities, most fail to address RV dysfunction. Therefore, improving RV function is a critical treatment goal. Exercise has emerged as an effective intervention for PAH, but the specific impact of swimming exercise on this disease and its associated pathological changes has been less extensively studied. In this study, we investigated the effects of swimming training (60 min/day, 5 days/week for 4 weeks) on monocrotaline (MCT; 60 mg/kg, i. p.)-induced PAH in rats. Our findings demonstrate that swimming significantly attenuates RV hypertrophy and reduces mean pulmonary arterial pressure (MPAP), mitigating the detrimental effects of PAH. Furthermore, we observed structural remodeling in the right ventricle, including increased myocardial necrosis, collagen deposition, and fibrosis-related protein expression. Swimming exercise training was found to reduce these pathological changes, suggesting a protective effect on the right ventricle. Mechanistically, our study revealed the crucial role of meta-inflammation in PAH and the anti-PAH effects of exercise. Swimming training attenuated macrophage accumulation, reduced serum inflammatory cytokines, and improved systemic and RV insulin sensitivity, highlighting its potential to modulate meta-inflammatory processes. In summary, our study suggests that swimming training exerts a beneficial effect on RV function and hypertrophy in MCT-induced PAH rats by targeting meta-inflammation. These results underscore the potential value of exercise-based rehabilitation as a complementary therapy for PAH patients.

Efficacy and safety of ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma: A meta-analysis.

OBJECTIVE: Meta-analysis was used to assess the efficacy and safety of ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma. METHODS: Randomized controlled studies on ultrasound-guided radiofrequency ablation combined with transhepatic artery embolization chemotherapy for hepatocellular carcinoma were searched in the databases of PubMed, Embase, Cochrane library, web of science with a search deadline of March 14, 2024. Data were analyzed using Stata 15.0. RESULT: Six randomized controlled studies involving 520 individuals were finally included, the results of meta-analysis showed that ultrasound-guided radiofrequency ablation combined with TACE can improve objective response rate [RR = 1.52, 95%CI (1.28, 1.81)], improve disease control rate [RR = 1.15, 95%CI (1.06, 1.24)], The survival rate [RR = 1.34, 95%CI (1.19,1.51)] did not increase adverse reactions [RR = 1.34, 95%CI (1.00,1.79)]. CONCLUSION: Based on the findings of the current study, ultrasound-guided radiofrequency ablation combined with TACE was found to improve the objective remission rate, disease control rate, and did not increase adverse events in patients with hepatocellular carcinoma.

Transcriptome and metabolome analyses provide insights into the fruit softening disorder of papaya fruit under postharvest heat stress.

Heat stress in summer causes softening disorder in papaya but the molecular mechanism is not clear. In this study, papaya fruit stored at 35 °C showed a softening disorder termed rubbery texture. Analysis of the transcriptome and metabolome identified numerous differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) between the fruit stored at 25 °C and 35 °C. The DEGs and DAMs related to lignin biosynthesis were upregulated, while those related to ethylene biosynthesis, sucrose metabolism, and cell wall degradation were downregulated under heat stress. Co-expression network analysis highlighted the correlation between the DEGs and metabolites associated with lignin biosynthesis, ethylene biosynthesis, and cell wall degradation under heat stress. Finally, the correlation analysis identified the key factors regulating softening disorder under heat stress. The study's findings reveal that heat stress inhibited papaya cell wall degradation and ethylene production, delaying fruit ripening and softening and ultimately resulting in a rubbery texture.

Multi-modal triggered-release sonodynamic/chemo/phototherapy synergistic nanocarriers for the treatment of colon cancer.

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100 nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

Integrative single-cell analysis of longitudinal t(8;21) AML reveals heterogeneous immune cell infiltration and prognostic signatures.

Introduction: Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis. Methods: Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research. Results: CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome. Discussion: In conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.

Logic Computing Field-Effect Transistors Based on a Monolayer WSe2 Homojunction for the Semi-adder and Decoder.

Two-dimensional reconfigurable field-effect transistors (FETs) are promising candidates for next-generation computing hardware. However, exploring the cascade design of FETs for logic computing remains challenging. Here, by using density functional theory combined with the nonequilibrium Green's function method, we design a 5 nm split-gate FET based on a monolayer WSe2 homojunction, which can implement dynamic polarity control in different gate configurations. The series array of two FETs shows a functional family of logic gates (NOR, AND, XOR, A̅B, and AB̅), and the semi-adder designed by the logic functions AND and XOR reduces the number of transistors by 66.7%. The parallel array of two FETs demonstrates reconfigurable logic gates with NAND/OR/A̅+B/A+B̅ quadruple functions, which can realize the decoding function of 00-11 in the decoder. The cascade design of the electrically tunable FETs helps to tackle the logic device downscaling and integration dilemmas.

Understanding the relationship between HCV infection and progression of kidney disease.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

EGPDI: identifying protein-DNA binding sites based on multi-view graph embedding fusion.

Mechanisms of protein-DNA interactions are involved in a wide range of biological activities and processes. Accurately identifying binding sites between proteins and DNA is crucial for analyzing genetic material, exploring protein functions, and designing novel drugs. In recent years, several computational methods have been proposed as alternatives to time-consuming and expensive traditional experiments. However, accurately predicting protein-DNA binding sites still remains a challenge. Existing computational methods often rely on handcrafted features and a single-model architecture, leaving room for improvement. We propose a novel computational method, called EGPDI, based on multi-view graph embedding fusion. This approach involves the integration of Equivariant Graph Neural Networks (EGNN) and Graph Convolutional Networks II (GCNII), independently configured to profoundly mine the global and local node embedding representations. An advanced gated multi-head attention mechanism is subsequently employed to capture the attention weights of the dual embedding representations, thereby facilitating the integration of node features. Besides, extra node features from protein language models are introduced to provide more structural information. To our knowledge, this is the first time that multi-view graph embedding fusion has been applied to the task of protein-DNA binding site prediction. The results of five-fold cross-validation and independent testing demonstrate that EGPDI outperforms state-of-the-art methods. Further comparative experiments and case studies also verify the superiority and generalization ability of EGPDI.

Magnetic-guided nanocarriers for ionizing/non-ionizing radiation synergistic treatment against triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the worst prognosis. Radiotherapy (RT) is one of the core modalities for the disease; however, the ionizing radiation of RT has severe side effects. The consistent development direction of RT is to achieve better therapeutic effect with lower radiation dose. Studies have demonstrated that synergistic effects can be achieved by combining RT with non-ionizing radiation therapies such as light and magnetic therapy, thereby achieving the goal of dose reduction and efficacy enhancement. METHODS: In this study, we applied FeCo NPs with magneto thermal function and phototherapeutic agent IR-780 to construct an ionizing and non-ionizing radiation synergistic nanoparticle (INS NPs). INS NPs are first subjected to morphology, size, colloidal stability, loading capacity, and photothermal conversion tests. Subsequently, the cell inhibitory and cellular internalization were evaluated using cell lines in vitro. Following comprehensive assessment of the NPs' in vivo biocompatibility, tumor-bearing mouse model was established to evaluate their distribution, targeted delivery, and anti-tumor effects in vivo. RESULTS: INS NPs have a saturation magnetization exceeding 72 emu/g, a hydrodynamic particle size of approximately 40 nm, a negatively charged surface, and good colloidal stability and encapsulation properties. INS NPs maintain the spectral characteristics of IR-780 at 808 nm. Under laser irradiation, the maximum temperature was 92 °C, INS NPs also achieved the effective heat temperature in vivo. Both in vivo and in vitro tests have proven that INS NPs have good biocompatibility. INS NPs remained effective for more than a week after one injection in vivo, and can also be guided and accumulated in tumors through permanent magnets. Later, the results exhibited that under low-dose RT and laser irradiation, the combined intervention group showed significant synergetic effects, and the ROS production rate was much higher than that of the RT and phototherapy-treated groups. In the mice model, 60% of the tumors were completely eradicated. CONCLUSIONS: INS NPs effectively overcome many shortcomings of RT for TNBC and provide experimental basis for the development of novel clinical treatment methods for TNBC.

Epidermal growth factor-loaded, dehydrated physical microgel-formed adhesive hydrogel enables integrated care of wet wounds.

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.

Guizhi Fuling Wan attenuates tetrachloromethane-induced hepatic fibrosis in rats via PTEN/AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Treatment options for hepatic fibrosis, a prevalent liver condition closely linked to cirrhosis, are currently limited. While Guizhi Fuling Wan (GFW), a pill derived from traditional Chinese herbs, has been reported to possess hepatoprotective properties, its therapeutic effect and mechanism in hepatic fibrosis remain elusive. AIM OF THE STUDY: This study aimed to evaluate the anti-fibrotic impact of GFW and its underlying mechanisms in both in vivo and in vitro settings. MATERIALS AND METHODS: Tetrachloromethane (CCl4) was used to induce hepatic fibrosis in male rats. In vitro, activation of hepatic stellate cells (HSCs) was triggered by platelet-derived growth factor-BB (PDGF-BB). In vivo, liver function, pathological alterations, and HSC activation were evaluated. Additionally, the impact of GFW on the activated phenotypes of Lieming Xu-2 (LX-2) cells was examined in vitro. Network pharmacology was employed to identify the potential targets of GFW in hepatic fibrosis. Lastly, the impact of GFW on the PTEN/AKT/mTOR pathway and PTEN ubiquitination in HSCs was investigated. RESULTS: GFW alleviated CCl4-induced liver damage and scarring in rats in a dose-dependent manner and suppressed HSC activation in vivo. Moreover, GFW inhibited the proliferation, migration, differentiation, and extracellular matrix (ECM) production of activated HSCs in vitro. GFW also promoted autophagy and apoptosis of HSCs. Meanwhile, network pharmacology and in vitro studies suggested that GFW inhibits the AKT/mTOR pathway by preventing PTEN degradation by suppressing ubiquitination. CONCLUSION: GFW attenuates Ccl4-induced hepatic fibrosis in male rats by regulating the PTEN/AKT/mTOR signaling pathway, positioning it as a potential candidate for the treatment of hepatic fibrosis.

CABP4 mutation in mice shows alteration in protein expression level and neuron discharge frequency.

Background: The calcium-binding protein 4 (CABP4) gene is a newly identified epilepsy-related gene that might be associated with a rare type of genetic focal epilepsy; that is, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In vitro, mutant CABP4 causes an increased inward flow voltage of calcium ions and a significant increase in the electrical signal discharge in hippocampus neurons; however, the role of CABP4 in epilepsy has not yet been specifically described, and there is not yet a CABP4 mutant animal model recapitulating the epilepsy phenotype. Methods: We introduced a human CABP4 missense mutation into the C57BL/6J mouse genome and generated a knock-in strain carrying a glycine-to-aspartic acid mutation in the gene. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to evaluate the CABP4 expression level. Slice patch-clamp recording was carried out on pyramidal cells of prefrontal cortex layers II and III. Results: The CABP4G155D/+ mutant mice were viable and born at an expected Mendelian ratio. Surprisingly, the heterozygous (HE) mice did not display either an abnormal appearance or an overt seizure phenotype, and there was no statistically significant difference between the HE and wild-type (WT) mice in terms of overall messenger RNA (mRNA) and protein expression. However, the HE mutant mice showed an imbalance in the amount of protein expressed in the brain regions. Additionally, the patch-clamp recordings from the HE mouse layer II/III cortical pyramidal cells revealed an increase in the frequency of micro-excitatory post-synaptic currents (mEPSCs) but no change in the amplitude was observed. Conclusions: The findings of this study suggest that the CABP4 p.G155D mutation might be one of the mechanisms underlying seizure onset.

Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs.

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma.

Using Large Language Models to Address Health Literacy in mHealth: Case Report.

The innate complexity of medical topics often makes it challenging to produce educational content for the public. Although there are resources available to help authors appraise the complexity of their content, there are woefully few resources available to help authors reduce that complexity after it occurs. In this case study, we evaluate using ChatGPT to reduce the complex language used in health-related educational materials. ChatGPT adapted content from the SmartSHOTS mobile application, which is geared toward caregivers of children aged 0 to 24 months. SmartSHOTS helps reduce barriers and improve adherence to vaccination schedules. ChatGPT reduced complex sentence structure and rewrote content to align with a third-grade reading level. Furthermore, using ChatGPT to edit content already written removes the potential for unnoticed, artificial intelligence-produced inaccuracies. As an editorial tool, ChatGPT was effective, efficient, and free to use. This article discusses the potential of ChatGPT as an effective, time-efficient, and open-source method for editing health-related educational materials to reflect a comprehendible reading level.

Ultrasound-targeted microbubble destruction facilitates cartilage repair through increased the migration of mesenchymal stem cells via HIF-1α-mediated glycolysis pathway in rats.

OBJECTIVE: Mesenchymal stem cells (MSCs) can treat osteoarthritis (OA), but their therapeutic efficacy is poor to date due to low migration efficiency. This study aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) could ameliorate cartilage repair efficiency through facilitating the migration of MSCs via hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis regulatory pathway in OA model rats. METHODS: OA rats were treated with MSCs alone or in combination with UTMD, respectively, for 4 weeks. Cartilage histopathology, MSCs migration efficiency, von Frey fiber thresholds, and the expression levels of collagen II and MMP-13 were measured. Further, MSCs were extracted from the bone marrow of rats, cocultured with osteoarthritic chondrocytes, transfected to siRNA-HIF-1α, and subjected to UTMD for 4 days. Glucose consumption, lactate production, and cell migration efficiency were assessed. The protein expression levels of HIF-1α, HK2, PKM2, and GLUT1 were measured, respectively. RESULTS: In OA rat model, NC-MSCs + UTMD improved migration efficiency, increased collagen II expression, decreased MMP-13 expression, and delayed osteoarthritis progression. Silencing HIF-1α attenuated the effects induced by UTMD. In vitro, UTMD led to increases in MSC activity and migration, glucose consumption, lactate production, and the protein expression of HIF-1α, HK2, PKM2, and GLUT1 expression, all of which were reversed upon HIF-1α silencing. CONCLUSION: UTMD enhances MSCs migration and improves cartilage repair efficiency through the HIF-1α-mediated glycolytic regulatory pathway, providing a novel therapy strategy for knee osteoarthritis.

Tissue-adhesive, stretchable and compressible physical double-crosslinked microgel-integrated hydrogels for dynamic wound care.

Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (∼940 kJ/m3) and compressive (∼270 kJ/m3) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care.

Pulmo-protection of long-term swimming exercise via improving insulin sensitivity in monocrotaline-induced pulmonary hypertensive rats.

Exercise has been recognized as an effective intervention in the treatment of pulmonary arterial hypertension (PAH), supported by numerous studies. However, the precise effects of exercise on pulmonary function remain to be fully elucidated. In this study, using a rat model of swimming exercise training and monocrotaline-induced PAH, we aimed to explore its impact on pulmonary morphology and function. Our investigations revealed that MCT-treated rats exhibited augmented mean pulmonary arterial pressure (MPAP) and pulmonary vascular remodeling, which can be attenuated by 4 weeks of swimming exercise training (60 min/day, 5 days/week). Notably, MCT-treated rats showed impaired pulmonary function, as manifested by decreased tidal volume and dynamic compliance, which were reversed by exercise training. Assessment of pulmonary substrate in PAH rats indicated a prominent pro-inflammatory substrate, evidenced by macrophage accumulation through quantitative immunohistological analysis of macrophage-like cell expression (CD68), and extracellular matrix remodeling, evaluated by Masson staining. Importantly, both the pro-inflammatory substrate and extracellular matrix remodeling were ameliorated by swimming exercise training. Additionally, serum biochemical analysis demonstrated elevated levels of low-density lipoprotein cholesterol and Apolipoprotein B following MCT treatment, which were reduced with exercise intervention. Moreover, exercise enhanced systemic insulin sensitivity in both MCT-treated and untreated rats. Notably, MCT and exercise treatment both decreased fasting blood glucose (FBG) levels in rats, whereas exercise training reinstated FBG levels to normal in MCT-treated rats. In summary, our study suggests that swimming exercise confers a pulmonary protective effect in MCT-induced PAH rats, highlighting the potential importance of exercise-based rehabilitation in the management of PAH.

Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

A bamboo 'PeSAPK4-PeMYB99-PeTIP4-3' regulatory model involved in water transport.

Water plays crucial roles in expeditious growth and osmotic stress of bamboo. Nevertheless, the molecular mechanism of water transport remains unclear. In this study, an aquaporin gene, PeTIP4-3, was identified through a joint analysis of root pressure and transcriptomic data in moso bamboo (Phyllostachys edulis). PeTIP4-3 was highly expressed in shoots, especially in the vascular bundle sheath cells. Overexpression of PeTIP4-3 could increase drought and salt tolerance in transgenic yeast and rice. A co-expression pattern of PeSAPK4, PeMYB99 and PeTIP4-3 was revealed by WGCNA. PeMYB99 exhibited an ability to independently bind to and activate PeTIP4-3, which augmented tolerance to drought and salt stress. PeSAPK4 could interact with and phosphorylate PeMYB99 in vivo and in vitro, wherein they synergistically accelerated PeTIP4-3 transcription. Overexpression of PeMYB99 and PeSAPK4 also conferred drought and salt tolerance in transgenic rice. Further ABA treatment analysis indicated that PeSAPK4 enhanced water transport in response to stress via ABA signaling. Collectively, an ABA-mediated cascade of PeSAPK4-PeMYB99-PeTIP4-3 is proposed, which governs water transport in moso bamboo.