Photoelectrochemical transistors based on semiconducting polymers: an emerging technology for future bioelectronics.

In recent years, organic electrochemical transistors (OECTs) have attracted widespread attention due to their significant advantages such as low-voltage operation, biocompatibility, and compatibility with flexible substrates. Organic photoelectrochemical transistors (OPECTs) are OECTs with photoresponse capabilities that achieve photoresponse and signal amplification in a single device, demonstrating tremendous potential in multifunctional optoelectronic devices. In this mini-review, we briefly introduce the channel materials and operation mechanisms of OECTs/OPECTs. Then different types of OPECTs are discussed depending on their device-architecture-related photoresponse generation. Following this, we summarize recent advances in OPECT applications across various fields including biomedical sciences, optoelectronics, and sensor technologies. Finally, we outline the current challenges and explore future research prospects, aiming at extending their further development and applications.

Malignant melanoma with liver, stomach, and duodenal metastasis.

Malignant melanoma (MM) is a common and highly invasive malignant tumor in clinical practice that is prone to occur in the skin and mucosa and prone to early metastasis. The common sites of metastasis are the liver, lungs, brain, etc. Metastatic gastrointestinal mucosa is relatively rare. Once metastasis occurs, the prognosis of patients is significantly worse. This article reports a case diagnosed as MM with liver, stomach, and duodenal metastasis by ultrasound-guided endoscopic puncture at Fengdu People's Hospital in Chongqing, with gastrointestinal discomfort as the initial symptom and a history of melanoma. Therefore, when a patient has a history of melanoma surgery and presents with digestive symptoms, it is necessary to consider the disease. Regular endoscopic screening should be performed, and early surgical treatment and postoperative chemotherapy combined with targeted therapy may improve patient prognosis and prolong patient survival.

Activation of TGR5 in the injured nerve site according to a prevention protocol mitigates partial sciatic nerve ligation-induced neuropathic pain by alleviating neuroinflammation.

ABSTRACT: Neuropathic pain is a pervasive medical challenge currently lacking effective treatment options. Molecular changes at the site of peripheral nerve injury contribute to both peripheral and central sensitization, critical components of neuropathic pain. This study explores the role of the G-protein-coupled bile acid receptor (GPBAR1 or TGR5) in the peripheral mechanisms underlying neuropathic pain induced by partial sciatic nerve ligation in male mice. TGR5 was upregulated in the injured nerve site and predominantly colocalized with macrophages. Perisciatic nerve administration of the TGR5 agonist, INT-777 according to a prevention protocol (50 µg/µL daily from postoperative day [POD] 0 to POD6) provided sustained relief from mechanical allodynia and spontaneous pain, whereas the TGR5 antagonist, SBI-115 worsened neuropathic pain. Transcriptome sequencing linked the pain relief induced by TGR5 activation to reduced neuroinflammation, which was further evidenced by a decrease in myeloid cells and pro-inflammatory mediators (eg, CCL3, CXCL9, interleukin [IL]-6, and tumor necrosis factor [TNF] α) and an increase in CD86-CD206+ anti-inflammatory macrophages at POD7. Besides, myeloid-cell-specific TGR5 knockdown in the injured nerve site exacerbated both neuropathic pain and neuroinflammation, which was substantiated by bulk RNA-sequencing and upregulated expression levels of inflammatory mediators (including CCL3, CCL2, IL-6, TNF α, and IL-1ß) and the increased number of monocytes/macrophages at POD7. Furthermore, the activation of microglia in the spinal cord on POD7 and POD14 was altered when TGR5 in the sciatic nerve was manipulated. Collectively, TGR5 activation in the injured nerve site mitigates neuropathic pain by reducing neuroinflammation, while TGR5 knockdown in myeloid cells worsens pain by enhancing neuroinflammation.

Rice Protein Peptides Alleviate Alcoholic Liver Disease via the PPARγ Signaling Pathway: Through Liver Metabolomics and Gut Microbiota Analysis.

Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of Alloprevotella and Alistipes, and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.

PTPN2 dephosphorylates STAT3 to ameliorate anesthesia-induced cognitive decline in aged rats by altering the microglial phenotype and inhibiting inflammation.

Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.

COVID-19 and sepsis-related excess mortality in the US during the first three years: A national-wide time series study.

The COVID-19 pandemic's global impact has been devastating, causing millions of deaths. Our study investigates excess sepsis-related mortality trends over three years during the pandemic. Using CDC's National Vital Statistics System data from January 2018 to March 2023, we projected sepsis-related deaths during the pandemic using a Poisson log-linear regression model. We compared observed versus predicted deaths and analyzed temporal trends by demographics and regions. Among the 753,160 deaths documented between March 2020 and March 2023, a significant downward trend was noted in sepsis-related mortality rates from March 2022 to March 2023, coinciding with the surge of the Omicron variant. The excess mortality rates were 170.6 per million persons (95% CI: 168.2-172.6), 167.5 per million persons (95% CI: 163.6-170.9), and 73.3 per million persons (95% CI: 69.4-76.6) in the first, second, and third years, respectively. Increased sepsis-related mortality was observed across all age subgroups, with the greatest increase noted in those aged 85 years and above compared to middle- and young-aged decedents. Disparities were also observed across racial/ethnic, sex/gender subgroups, and geographic regions. This study highlights the effectiveness of current policies and prevention measures in response to the long-term circulating of SARS-CoV-2 in the community.

Upregulation of ARHGAP9 is correlated with poor prognosis and immune infiltration in clear cell renal cell carcinoma.

Rho GTPase activating protein (ARHGAP) family genes play critical roles in the onset and progression of human cancer. Rho GTPase activating protein 9 (ARHGAP9) is upregulated in various tumors. However, far too little attention has been paid to the prognostic value of ARHGAP9 and correlation with immune infiltration in clear cell renal cell carcinoma (ccRCC). Our aim is to evaluate the prognostic significance of ARHGAP9 expression and its correlation with immune infiltration in ccRCC. Transcriptional expression profiles of ARHGAP9 between ccRCC tissues and normal tissues were downloaded from The Cancer Genome Atlas. The ARHGAP9 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium. Receiver operating characteristic curve was used to differentiate ccRCC from adjacent normal tissues. The Kaplan-Meier method was conducted to assess the effect of ARHGAP9 on survival. Protein-protein interaction networks were constructed by the STRING. Functional enrichment analyses were performed using the "ClusterProfiler" package. The immune infiltration patterns were evaluated via the tumor immune estimation resource 2.0 and Tumor-Immune System Interaction Database. ARHGAP9 expression was substantially higher in ccRCC tissues than in adjacent normal tissues. Increased ARHGAP9 mRNA expression was shown to be linked to high TNM stage and lymph node metastases. The diagnostic value of ARHGAP9 gene expression data was assessed using receiver operating characteristic curve analysis. The survival analysis module of GEPIA2 and the Kaplan-Meier plotter both showed ccRCC patients with high-ARHGAP9 had a worse prognosis than those with low-ARHGAP9. Correlation analysis indicated ARHGAP9 mRNA expression was significantly correlated with tumor purity and immune infiltrates. These findings demonstrate that upregulated ARHGAP9 indicates poor prognosis and immune infiltration in ccRCC. The current findings suggest that ARHGAP9 can be an effective biomarker and potential therapeutic strategy for ccRCC.

The chromodomain protein CDYL confers forebrain identity to human cortical organoids by inhibiting neuronatin.

Fate determination of neural stem cells (NSCs) is crucial for cortex development and is closely linked to neurodevelopmental disorders when gene expression networks are disrupted. The transcriptional corepressor chromodomain Y-like (CDYL) is widely expressed across diverse cell populations within the human embryonic cortex. However, its precise role in cortical development remains unclear. Here, we show that CDYL is critical for human cortical neurogenesis and that its deficiency leads to a substantial increase in gamma-aminobutyric acid (GABA)-ergic neurons in cortical organoids. Subsequently, neuronatin (NNAT) is identified as a significant target of CDYL, and its abnormal expression obviously influences the fate commitment of cortical NSCs. Cross-species comparisons of CDYL targets unravel a distinct developmental trajectory between human cortical organoids and the mouse cortex at an analogous stage. Collectively, our data provide insight into the evolutionary roles of CDYL in human cortex development, emphasizing its critical function in maintaining the fate of human cortical NSCs.

Efficient Photoelectrocatalytic Reduction of CO2 to Selectively Produce Ethanol Using FeS2/TiO2 p-n Heterojunction Photoelectrodes.

Herein, the FeS2/TiO2 p-n heterojunction was first utilized as a photoelectrode for the PEC reduction of CO2 to selectively produce ethanol. The FeS2/TiO2 photoelectrode was fabricated through electrochemical anodization, electrodeposition, and vulcanization methods. The impact of the FeS2 loading amount and applied bias on the PEC performance was investigated. The behavior of photocurrent polarity reverse is observed depending on the FeS2 loading amount, which is related to the energy band structure of the semiconductor/electrolyte interface. The active sites for ethanol production were identified on TiO2 nanotubes rather than on the FeS2 surface. Incorporation of FeS2 not only broadened the visible light absorption range but also formed a p-n heterojunction with TiO2. FeS2/TiO2 with an electrodeposition time of 15 min exhibits the highest ethanol yield of 1170 µmol L-1 cm-2 for 3.5 h of reaction under ultraviolet-visible (UV-Vis) illumination at an applied bias of -0.7 V. Compared to TiO2, FeS2/TiO2 showed significantly higher ethanol yield due to its appropriate loading amount of FeS2 and the synergistic effect of strong UV-Vis light absorption and efficient separation and transfer of charge carriers at the p-n junction.

Organic Nano-Junctions: Linking Nanomorphology and Charge Transport in Organic Semiconductor Nanoparticles for Organic Photovoltaic Devices.

In this study, innovative nanoscale devices are developed to investigate the charge transport in organic semiconductor nanoparticles. Using different steps of lithography techniques and dielectrophoresis, planar organic nano-junctions are fabricated from which hole mobilities are extracted in a space charge-limited current regime. Subsequently, these devices are used to investigate the impact of the composition and morphology of organic semiconductor nanoparticles on the charge mobilities. Pure donor nanoparticles and composite donor:acceptor nanoparticles with different donor compositions in their shell are inserted in the nanogap electrode to form the nano-junctions. The results highlight that the hole mobilities in the composite nanoparticles decrease by two-fold compared to pure donor nanoparticles. However, no significant change between the two kinds of composite nanoparticle morphologies is observed, indicating that conduction pathways for the holes are as efficient for donor proportion in the shell from 40% to 60%. Organic photovoltaic (OPV) devices are fabricated from water-based colloidal inks containing the two composite nanoparticles (P3HT:eh-IDTBR and P3HT:o-IDTBR) and no significant change in the performances is observed in accordance with the mobility results. Through this study, the performance of OPV devices have been succesfully correlated to the transport properties of nanoparticles having different morphology via innovative nanoscale devices.

Electrical Control of Magnetic Resonance in Phase Change Materials.

Metal-insulator transitions (MITs) in resistive switching materials can be triggered by an electric stimulus that produces significant changes in the electrical response. When these phases have distinct magnetic characteristics, dramatic changes in the spin excitations are also expected. The transition metal oxide La0.7Sr0.3MnO3 (LSMO) is a ferromagnetic metal at low temperatures and a paramagnetic insulator above room temperature. When LSMO is in its metallic phase, a critical electrical bias has been shown to lead to an MIT that results in the formation of a paramagnetic resistive barrier transverse to the applied electric field. Using spin-transfer ferromagnetic resonance spectroscopy, we show that even for electrical biases less than the critical value that triggers the MIT, there is magnetic phase separation, with the spin-excitation resonances varying systematically with applied bias. Therefore, voltage-triggered MITs in LSMO can alter magnetic resonance characteristics, offering an effective method for tuning synaptic weights in neuromorphic circuits.

Fe Single Atoms Anchored on N-doped Mesoporous Carbon Microspheres for Promoted Oxygen Reduction Reaction.

Fe single atoms (Fe SAs) based catalysts have received much attention in electrocatalytic oxygen reduction reaction (ORR) due to its low-cost and high activity. Yet, the facile synthesis of efficient and stable Fe SAs catalysts is still challenging. Here, we reported a Fe SAs anchored on N-doped mesoporous carbon microspheres (NC) catalyst via spraying drying and pyrolysis processes. The highly active Fe SAs are uniformly distributed on the NC matrix, which prevented the aggregation benefiting from the enhanced Fe-N bonds. Also, the mesoporous carbon structure is favorable for fast electron and mass transfer. The optimized Fe@NC-2-900 catalyst shows positive half wave potential (E1/2=0.86 V vs reversible hydrogen electrodes (RHE)) and starting potential (Eonset=0.98 V vs RHE) in ORR, which is comparable to the commercial Pt/C catalyst (E1/2=0.87 V, Eonset=1.08 V vs RHE). Outstanding stability with a current retention rate of 92.5 % for 9 hours and good methanol tolerance are achieved. The assembled zinc-air batteries showed good stability up to 500 hours at a current density of 5 mA cm-2. This work shows potentials of Fe SAs based catalysts for the practical application in ORR and pave a new avenue for promoting their catalytic performances.

Achieving Immune Activation by Suppressing the IDO1 Checkpoint with Sono-Targeted Biobromination for Antitumor Combination Immunotherapy.

Indoleamine-2,3-dioxygenase-1 (IDO1) pathogenically suppresses immune cell infiltration and promotes tumor cell immune escape by overmetabolizing tryptophan to N-formyl kynurenine in the tumor microenvironment (TME). However, it remains challenging for IDO1 immune checkpoint inhibitors to achieve a significant potency of progression-free survival. Here, we developed a breakthrough in IDO1 inhibition by sono-targeted biobromination reaction using immunostimulating hypobromic-P-phenylperoxydibenzoic acid-linked metallic organic framework nanomedicine (H-MOF NM) to remodel the TME from debrominated hypoxia into hypobromated normoxia and activate the IDO1 immune pathway with in vitro and in vivo remarkable antitumor efficacy. H-MOF NM contains Br+ and O- active ingredients with an enlarged band gap to deactivate IDO1 through an innovative biochemical mechanism, taking control over brominating IDO1 amino acid residues at the active sites in the remodeled TME and subsequently activating the immune response, including DC maturation, T-cell activation, and macrophage polarization. Importantly, the H-MOF NM achieves multiple immune responses with high tumor regression potency by combination sono-immunotherapy. This study describes an excellent IDO1 inhibition strategy through the development of immune biobrominative H-MOF nanomedicine and highlights efficient combination immunotherapy for tumor treatment.

Microglial activation and polarization in type 2 diabetes-related cognitive impairment: A focused review of pathogenesis.

Microglia, as immune cells in the central nervous system, are closely related to cognitive impairment associated with type 2 diabetes (T2D). Preliminary explorations have investigated the relationship between T2D-related cognitive impairment and the activation and polarization of microglia. This review summarizes the potential mechanisms of microglial activation and polarization in the context of T2D. It discusses central inflammatory responses, neuronal apoptosis, amyloid-ß deposition, and abnormal phosphorylation of Tau protein mediated by microglial activation and polarization, exploring the connections between microglial activation and polarization and T2D-related cognitive impairment from multiple perspectives. Additionally, this review provides references for future treatment targeting microglia in T2D-related cognitive impairment and for clinical translation.

Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain.

Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.

Rice Protein Peptides Ameliorate DSS-Induced Cognitive Impairment and Depressive Behavior in Mice by Modulating Phenylalanine Metabolism and the BDNF/TRKB/CREB Pathway.

Rice protein peptide (RPP) has been reported to alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis, but its potential protective effect and fundamental neurobiological mechanisms against DSS-induced inflammatory bowel disease (IBD), coupled with depression and cognitive impairment, remain unclear. In this study, RPP treatment in DSS-induced mice inhibited decreases in body weight and colon length and improved intestinal barrier function and behavioral performance. RPP treatment enhanced phenylalanine and tyrosine metabolism in the brains of mice, and it upregulated metabolites such as l-dopa, phenylethylamine, and 3,4-dihydroxyphenylacetate. Additionally, RPP treatment enhanced the brain-derived neurotrophic factor (BDNF) by upregulating the BDNF/TrkB/CREB signaling pathway. Spearman's correlation analysis revealed that the phenylalanine and tyrosine contents in the brain were significantly negatively correlated with the BDNF/TrkB/CREB signaling pathway and behavioral performance. In conclusion, this study suggested that RPP may serve as a unique nutritional strategy for preventing IBD and its associated cognitive impairment and depression symptoms.

Ferroptosis in Cognitive Impairment Associated with Diabetes and Alzheimer's Disease: Mechanistic Insights and New Therapeutic Opportunities.

Cognitive impairment associated with diabetes and Alzheimer's disease has become a major health issue affecting older individuals, with morbidity rates growing acutely each year. Ferroptosis is a novel form of cell death that is triggered by iron-dependent lipid peroxidation. A growing body of evidence suggests a strong correlation between the progression of cognitive impairment and diabetes, Alzheimer's disease, and ferroptosis. The pharmacological modulation of ferroptosis could be a promising therapeutic intervention for cognitive impairment associated with diabetes and Alzheimer's disease. In this review, we summarize evidence on ferroptosis in the context of cognitive impairment associated with diabetes and Alzheimer's disease and provide detailed insights into the function and potential action pathways of ferroptosis. Furthermore, we discuss the therapeutic importance of natural ferroptosis products in improving the cognitive impairment associated with diabetes and Alzheimer's disease and provide new insights for clinical treatment.

Mechanisms of bacterial and fungal community assembly in leaf miners during transition from natural to laboratory environments.

Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.

Histone modifications in hypoxic ischemic encephalopathy: Implications for therapeutic interventions.

Hypoxic-ischemic encephalopathy (HIE) is a brain injury induced by many causes of cerebral tissue ischemia and hypoxia. Although HIE may occur at many ages, its impact on the neonatal brain is greater because it occurs during the formative stage. Recent research suggests that histone modifications may occur in the human brain in response to acute stress events, resulting in transcriptional changes and HIE development. Because there are no safe and effective therapies for HIE, researchers have focused on HIE treatments that target histone modifications. In this review, four main histone modifications are explored, histone methylation, acetylation, phosphorylation, and crotonylation, as well as their relevance to HIE. The efficacy of histone deacetylase inhibitors in the treatment of HIE is also explored. In conclusion, targeting histone modifications may be a novel strategy for elucidating the mechanism of HIE, as well as a novel approach to HIE treatment.

Robotic left colectomy and intracorporeal overlap anastomosis for descending-sigmoid cancer with da Vinci Xi® robotic platform-a video vignette.

This video vignette illustrates the application of the da Vinci Xi® robotic platform for robotic left colectomy and intracorporeal overlap anastomosis in a 51-year-old patient diagnosed with sigmoid-descending colon junction cancer. Emphasizing the advantages of robotic surgery in colorectal procedures, the video showcases a complete mesocolic excision, involving steps such as medial-to-lateral dissection, mobilization of the splenic flexure, ligation of the left colic and sigmoid arteries, and resection of an abdominal wall nodule. The presentation highlights the surgical precision and efficiency achieved, including minimal blood loss and no complications, with an operation time of 190 min. The postoperative outcome was favorable, with the patient discharged on the eighth day and subsequent management involving chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for stage pT4bN1aM1c moderately differentiated adenocarcinoma. This case underscores the enhanced capabilities of robotic platforms in complex colorectal surgeries, particularly in achieving cytoreductive surgery (CRS) and ensuring anastomosis safety with improved R0 resection rates.