The association between acute kidney injury and dysglycaemia in critically ill patients with and without diabetes mellitus: a retrospective single-center study.

BACKGROUND: Critically ill patients in the intensive care unit (ICU) often experience dysglycaemia. However, studies investigating the link between acute kidney injury (AKI) and dysglycaemia, especially in those with and without diabetes mellitus (DM), are limited. METHODS: We used the Medical Information Mart for Intensive Care IV database to investigate the association between AKI within 7 days of admission and subsequent dysglycaemia. The primary outcome was the occurrence of dysglycaemia (both hypoglycemia and hyperglycemia) after 7 days of ICU admission. Logistic regression analyzed the relationship between AKI and dysglycaemia, while a Cox proportional hazards model estimated the long-term mortality risk linked to the AKI combined with dysglycaemia. RESULTS: A cohort of 20,008 critically ill patients were included. The AKI group demonstrated a higher prevalence of dysglycaemia, compared to the non-AKI group. AKI patients had an increased risk of dysglycaemia (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.41-1.65), hypoglycemia (aOR 1.56, 95% CI 1.41-1.73), and hyperglycemia (aOR 1.53, 95% CI 1.41-1.66). In subgroup analysis, compared to DM patients, AKI showed higher risk of dysglycaemia in non-DM patients (aOR: 1.93 vs. 1.33, Pint<0.01). Additionally, the AKI with dysglycaemia group exhibited a higher risk of long-term mortality compared to the non-AKI without dysglycaemia group. Dysglycaemia also mediated the relationship between AKI and long-term mortality. CONCLUSION: AKI was associated with a higher risk of dysglycaemia, especially in non-DM patients, and the combination of AKI and dysglycaemia was linked to higher long-term mortality. Further research is needed to develop optimal glycemic control strategies for AKI patients.

Correlation between blood pressure and mortality in older critically ill patients: Insights from a large intensive care unit database.

OBJECTIVES: The study aimed to investigate the relationship between blood pressure (BP) levels and mortality among critically ill older adults in the intensive care unit (ICU), establish optimal BP target for this population, and assess the mediating effect of severe malnutrition on BP-related mortality. METHODS: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.2 database, focusing on critically ill patients aged 80 years and older. The analysis included various BP parameters, such as systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). RESULTS: The study cohort comprised 14,660 critically ill patients, of whom 1558 (10.6 %) experienced ICU mortality and 2493 (17.0 %) experienced in-hospital mortality. Lower BP levels (SBP ≤ 112 mmHg; DBP ≤ 53 mmHg; MAP ≤65 mmHg), were associated with an increased risk of both ICU and in-hospital mortality. Notably, only reduced SBP levels were linked to a higher risk of 1-year mortality, with an adjusted hazard ratio 1.13 (95 % confidence interval 1.05 to 1.23). Additionally, severe malnutrition was identified as a mediator in the relationship between low BP levels and ICU mortality, with BP levels positively correlated with prognostic nutritional indexes. CONCLUSION: Among critically ill older adults, lower BP levels are significantly associated with higher risks of ICU and in-hospital mortality, while reduced SBP levels are linked to 1-year mortality. These findings emphasize the importance of assessing nutritional status in older ICU patients with low BP levels to potentially mitigate mortality risk.

Nickel-Iron Layered Double Hydroxides/Nickel Sulfide Heterostructured Electrocatalysts on Surface-Modified Ti Foam for the Oxygen Evolution Reaction.

Electrochemical approaches for generating hydrogen from water splitting can be more promising if the challenges in the anodic oxygen evolution reaction (OER) can be harnessed. The interface heterostructure materials offer strong electronic coupling and appropriate charge transport at the interface regions, promoting accessible active sites to prompt kinetics and optimize the adsorption-desorption of active species. Herein, we have designed an efficient multi-interface-engineered Ni3Fe1 LDH/Ni3S2/TW heterostructure on in situ generated titanate web layers from the titanium foam. The synergistic effects of the multi-interface heterostructure caused the exposure of rich interfacial electronic coupling, fast reaction kinetics, and enhanced accessible site activity and site populations. The as-prepared electrocatalyst demonstrates outstanding OER activity, demanding a low overpotential of 220 mV at a high current density of 100 mA cm-2. Similarly, the designed Ni3Fe1 LDH/Ni3S2/TW electrocatalyst exhibits a low Tafel slope of 43.2 mV dec-1 and excellent stability for 100 h of operation, suggesting rapid kinetics and good structural stability. Also, the electrocatalyst shows a low overpotential of 260 mV at 100 mA cm-2 for HER activity. Moreover, the integrated electrocatalyst exhibits an incredible OER activity in simulated seawater with an overpotential of 370 mV at 100 mA cm-2 and stability for 100 h of operation, indicating good OER selectivity. This work might benefit further fabricating effective and stable self-sustained electrocatalysts for water splitting in large-scale applications.

Battery-Free and Multifunctional Microfluidic Janus Wound Dressing with Biofluid Management, Multi-Indicator Monitoring, and Antibacterial Properties.

The sophisticated environment of chronic wounds, characterized by prolonged exudation and recurrent bacterial infections, poses significant challenges to wound recovery. Recent advancements in multifunctional wound dressings fall short of providing comprehensive, accurate, and comfortable treatment. To address these issues, a battery-free and multifunctional microfluidic Janus wound dressing (MM-JWD) capable of three functions, including exudate management, antibacterial properties, and multiple indications of wound infection detection, has been developed. During the treatment, the fully soft microfluidic Janus membrane not only demonstrated stable unidirectional fluid transport capabilities under various skin deformations for a longer period but also provided antibacterial effects through surface treatment with chitosan quaternary ammonium salts and poly(vinyl alcohol). Furthermore, integrating multiple colorimetric sensors within the Janus membrane's microchannels and a dual-layer structure enabled simultaneous monitoring of the wound's pH, uric acid, and temperature. The monitoring was facilitated by smartphone recognition of color changes in the sensors. In vivo and in vitro tests confirmed the exudate management, antibacterial, and sensing capabilities of the MM-JWD, proving its efficacy in monitoring and promoting the healing of wounds. Overall, this study provides a valuable method for the design of multifunctional wound dressings for chronic wound care.

Editorial Commentary Failure following biceps long head tenodesis includes Popeye sign, cramping, and tendon migration.

The long head of the biceps tendon (LHBT) is often referred to as a "pain generator" around the shoulder, and tenodesis of the LHBT is a commonly used surgical method for treating pathologies of the tendon. Current literature indicates that tenodesis of the LHBT can lead to reduced pain, improved shoulder function, and a low failure rate. However, the definition of failure following LHBT tenodesis varies. Clinically, postoperative cramping is generally considered a sign of treatment failure, while the appearance of a Popeye sign is usually regarded as a mechanical failure. In addition, recent research shows increased migration of the tenodesed biceps tendon is associated with inferior clinical outcome. While some degree of tendon migration can occur as a physiological response to the shortening of the muscle-tendon unit, excessive migration may be caused by loosening at the tendon-implant interface or suture cut-through. This can lead to painful cramping or weakness in the shoulder. The findings explain why some patients experience cramping or pain in the bicipital groove after LHBT tenodesis, even in the absence of a Popeye sign. When evaluating biomechanical studies, it's essential to consider not only the ultimate load failure but also the elongation that occurs with cyclic loading. Biomechanical study shows cyclic displacement was greater in both all-suture anchor and all-suture button groups versus interference screw fixation. If this results in clinical tendon migration, these fixation methods might result in inferior outcome, illustrating the importance of cyclic loading.

Alpinia officinarum Hance extract relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis.

Sepsis is generally triggered by a dysfunctional host response to infection, and it can result in life-threatening organ dysfunction. Alpinia officinarum Hance (AO) exhibits regulatory functions in some diseases. However, whether AO extract (AOE) plays a promoting role in sepsis--triggered myocardial injury is unclear. This study was aimed at investigating the regulatory effects of AOE on myocardial ferroptosis and inflammation in sepsis, and the regulation effects on the lncRNA MIAT/TRAF6/NF-κB axis. Lipopolysaccharide (LPS) was used to treat mice for establishing an in vivo sepsis model. The pathological changes in heart tissues were observed through hematoxylin-eosin (HE) staining. The levels of CK-MB, cTnl, MDA, SOD, IL-1ß, IL-18, IL-6, and TNF-α in serum were detected through enzyme-linked immunosorbent assay (ELISA). The level of Fe2+ was assessed, and the protein expressions (ACSL4, GPX4, TRAF6, p-P65, and P65) were examined through western blot. The expressions of lncRNA MIAT and TRAF6 were measured through real-time quantitative polymerase chain reaction (RT-qPCR). Our results demonstrated that AOE treatment ameliorated sepsis-triggered myocardial damage by reducing the disordered cardiomyocytes, the destroyed sarcolemma, and the CK-MB and cTnl levels. In addition, AOE treatment inhibited sepsis-induced myocardial ferroptosis and inflammation by regulating Fe2+, ACSL4, GPX4, IL-1ß, IL-18, IL-6, and TNF-α levels. Moreover, the improvement effect of AOE was strengthened with the increase in the dose of AOE (25, 50, 100 mg/kg). It was also revealed that AOE treatment retarded the lncRNA MIAT/TRAF6/NF-κB axis. Rescue assays manifested that overexpression of MIAT reduced the cardioprotective effect of AOE. In conclusion, AOE relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis. These findings may provide a potential therapeutic drug for the treatment of sepsis.

Case report: A rare heterozygous Hb CS with heterozygous HbE in a family with thalassemia in China.

Thalassemia is a hemoglobin disease characterized by reduced or complete absence of the production of the α/ß globin gene. Currently, the detection of ß-thalassemia carriers is based on differences in blood cell parameters. However, ß-thalassemia carriers cannot be distinguished from α- and ß-thalassemia co-inherited carriers based solely on hematological findings, and the differential diagnosis must rely on molecular diagnosis. We report a 32-year-old male from Yunnan Province, who had abnormal hemoglobin E without obvious anemia. A rare αCS (CD142, TAA→CAA) combined with a ßE (CD26, GAG→AAG) double heterozygous mutation was identified in the proband by PCR-reverse dot blot (PCR-RDB) and DNA sequencing. Additionally, a family lineage analysis was performed. This study complements the spectrum of rare thalassemia gene variants and is critical for clinical genetic counseling.

Investigating the influence of varied ratios of red and far-red light on lettuce (Lactuca sativa): effects on growth, photosynthetic characteristics and chlorophyll fluorescence.

Far red photon flux accelerates photosynthetic electron transfer rates through photosynthetic pigments, influencing various biological processes. In this study, we investigated the impact of differing red and far-red light ratios on plant growth using LED lamps with different wavelengths and Ca1.8Mg1.2Al2Ge3O12:0.03Cr3+ phosphor materials. The control group (CK) consisted of a plant growth special lamp with 450 nm blue light + 650 nm red light. Four treatments were established: F1 (650 nm red light), F2 (CK + 730 nm far-red light in a 3:2 ratio), F3 (650 nm red light + 730 nm far-red light in a 3:2 ratio), and F4 (CK + phosphor-converted far-red LED in a 3:2 ratio). The study assessed changes in red and far-red light ratios and their impact on the growth morphology, photosynthetic characteristics, fluorescence characteristics, stomatal status, and nutritional quality of cream lettuce. The results revealed that the F3 light treatment exhibited superior growth characteristics and quality compared to the CK treatment. Notably, leaf area, aboveground fresh weight, vitamin C content, and total soluble sugar significantly increased. Additionally, the addition of far-red light resulted in an increase in stomatal density and size, and the F3 treatments were accompanied by increases in net photosynthetic rate (Pn), transpiration rate (Tr), intercellular CO2 concentration (Ci), and stomatal conductance (Gs). The results demonstrated that the F3 treatment, with its optimal red-to-far-red light ratio, promoted plant growth and photosynthetic characteristics. This indicates its suitability for supplementing artificial light sources in plant factories and greenhouses.

Xuetongsu ameliorates synovial inflammatory hyperplasia in rheumatoid arthritis by inhibiting JAK2/STAT3 and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Synovial inflammatory hyperplasia is the key pathological process that leads to further joint damage in rheumatoid arthritis (RA) progress. Kadsura heteroclita (Roxb) Craib, also called Xuetong in Chinese Tujia ethnomedicine, is utilized for its medicinal properties, including promoting blood circulation, dispelling "wind evil", and relieving "damp evil". It has been used in the treatment of arthralgia and RA, within Tujia ethnomedicinal practices. Xuetongsu (XTS), the main component of Xuetong, has been shown to inhibit the proliferation of RA fibroblast-like synovial cells (RAFLS) cells. However, the molecular mechanism of XTS in RA treatment requires further investigation. AIM OF THE STUDY: To observe the therapeutic effect of XTS on synovial inflammatory hyperplasia in rheumatoid arthritis, focusing on its underlying molecular mechanisms involving the janus kinase 2 (JAK2)/transducer/activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) signaling pathways. MATERIALS AND METHODS: Protein-protein interaction (PPI) and molecular docking were used to find the main targets of XTS treatment for RA. In lipopolysaccharide (LPS)-induced RAFLS and RAW264.7 cells in vitro models, the levels of inflammatory cytokines were analyzed using enzyme linked immunosorbent assay (ELISA), and the expression of JAK2, STAT3, and NF-κB signaling pathways, as well as cyclooxygenase-2 (COX-2), were analyzed through western blotting test. A hemolysis assay was used to certify the biosecurity of XTS. A model of adjuvant arthritis (AIA) was established in 40 male rats, and different doses of XTS were administered, followed by an automatic blood routine, ELISA assay, hematoxylin and eosin (H&E) staining, and radiological analysis of the effect of no XTS on blood cytokines, histological changes, and improvement of posterior paw bone destruction in AIA rats. The protein levels of inflammatory cytokines were analyzed by immunofluorescence, immunohistochemistry, or Western blot. Finally, H&E staining was used to detect the damage of XTS on the heart, liver, spleen, lung, and kidney of AIA rats. RESULTS: Our results demonstrate that XTS effectively inhibited LPS-induced inflammatory responses in RAFLS and RAW264.7 cells by modulating the JAK2/STAT3 and NF-κB signaling pathways. Moreover, XTS administration in the AIA rats model significantly ameliorated paw swelling. Histological analysis revealed that XTS also suppressed the inflammatory response in paw tissue by modulating the JAK2/STAT3 and NF-κB signaling pathways. Importantly, during the treatment, XTS exhibited excellent safety profiles, as it did not induce any abnormalities in blood routine parameters or cause organ damage in the rats. CONCLUSIONS: Our findings highlight XTS as a promising natural agent for inhibiting synovial hyperplasia in RA. XTS holds great potential as an unprecedented natural agent for developing novel therapeutic strategies to target synovial hyperplasia in RA.

iPLA2ß regulates the dual effects of arachidonic acid in thyroid cancer.

BACKGROUND: Abnormal arachidonic acid metabolism in the tumor microenvironment is closely related to cancer progression; however, thyroid cancer was rarely researched. METHODS: Through lipidomic analysis, we disclosed that dysregulated arachidonic acid metabolism plays dual effects on thyroid cancer. The promoting role of arachidonic acid in the progression of thyroid cancer cells was evaluated utilizing cell viability (CCK-8 assay) and transwell invasion assays, confirmed by corresponding inhibitors. Lipid peroxidation and the use of various cell death inhibitors confirmed that arachidonic acid confers vulnerability to ferroptosis in thyroid cancer. The roles of arachidonic acid and ferroptosis inducer in thyroid cancer were assessed in a xenograft mouse model. RESULTS: On one hand, arachidonic acid promotes the progression of thyroid cancer through the cyclooxygenase/prostaglandin pathway; on another hand, arachidonic acid confers vulnerability to ferroptosis through lipoxygenases. Moreover, iPLA2ß drives converse roles of arachidonic acid between cancer-progression and ferroptosis vulnerability through releasing free arachidonic acid from the cell membrane. Finally, we confirmed high arachidonic acid diet promotes the development of thyroid cancer in vivo, whereas ferroptosis inducer sulfasalazine dramatically reduced tumor growth of mice with feeding arachidonic acid. CONCLUSIONS: Our research demonstrated the roles of iPLA2ß in conversing dual effects of arachidonic acid in thyroid cancer and provides ferroptosis inducer as a potential therapeutic strategy.

Enhanced oxygen evolution reaction activity on two-dimensional vdW ferromagnetic Cr2Ge2Te6 through synergism between two active sites.

To design an efficient, low-cost, and easily recoverable oxygen evolution reaction (OER) electrocatalyst, this work focuses on two-dimensional vdW ferromagnetic Cr2Ge2Te6. Based on the density functional theory (DFT) calculations, the adsorption of oxygen-containing intermediates during the OER process will gradually decrease the bandgap of Cr2Ge2Te6, thus increasing its electrical conductivity. More importantly, we propose a two active sites synergistic mechanism through a hydroxyl-boosted pathway. With the combined action of the two active sites, the binding between the oxygen-containing intermediates and the surfaces is enhanced. The enhancement comes from dramatic charge-transfer-induced Te-3p and O-2p orbital enhancement. As a result, the overpotential of the OER reduces from 1.25 to 0.59 V. We hope these findings will pave the way for more experimental and theoretical research to explore the potential applications of two-dimensional vdW ferromagnetic materials in energy storage and conversion.

Sarcopenia and cognitive impairment in older adults: Long-term prognostic implications based on the National Health and Nutrition Examination Survey (2011-2014).

AIMS: The relationship between sarcopenia and cognitive impairment in older adults remains contentious. This study investigates this association and examines the long-term prognosis for individuals with both conditions. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, this study focuses on the correlation between sarcopenia and cognitive impairment, as well as the extended prognosis for individuals managing these conditions. RESULTS: The study cohort comprised 2890 participants, with 648 (22.4 %) diagnosed with sarcopenia. Multivariable logistic regression analysis identified a significant association between sarcopenia and an increased risk of cognitive impairment (adjusted odds ratio [aOR]: 1.68, 95 % confidence interval [CI]: 1.30-2.17). Over a median follow-up period of 48 months, 200 individuals (6.9 %) succumbed to cardiovascular and cerebrovascular diseases (CCVDs), including hypertension, congestive heart failure, coronary artery disease, and stroke, as well as Alzheimer's disease (AD). Participants had comorbid conditions such as CCVDs and diabetes mellitus. Kaplan-Meier survival analysis and the Cox proportional hazards model indicated that individuals with both sarcopenia and cognitive impairment had the highest mortality risk from CCVDs and AD (adjusted hazard ratio [aHR]: 2.73, 95 % CI: 1.48-5.02). Individuals with sarcopenia and comorbidities exhibited a higher mortality risk from CCVDs or AD compared to those without sarcopenia but with comorbidities (aHR: 2.71, 95 % CI: 1.37-5.37). CONCLUSION: Sarcopenia is independently associated with cognitive impairment. Older adults with both sarcopenia and cognitive impairment or concurrent comorbidities face increased mortality risks from CCVDs or AD compared to their healthy counterparts.

Chitosan/agarose hydrogel dressing: pH response real-time monitoring and chemo-/photodynamic therapy synergistic treatment of infected wounds.

The early diagnosis and real-time monitoring of bacterial infections are of great significance for the establishment of integrated diagnosis and treatment systems. In this study, a pH-responsive smart hydrogel patch system, named CABP, was developed to monitor and treat wound infections. CABP has a sandwich structure, with non-woven fabric/chitosan (NF/CS) as the intermediate skeleton layer, Agarose/chitosan/Bromothymol Blue (AG/CS/BTB) hydrogel as the detection layer, and Agarose/chitosan/phthalocyanine (AG/CS/Pc) hydrogel as the treatment layer. When Staphylococcus aureus (S. aureus) infection occurs, the pH of the environment decreases, which triggers the CABP to change from its original blue color to yellow, achieving an intuitive visual transformation. Moreover, the hydrogel patch showed a significant inhibition rate of up to 99.99971 % against S. aureus under 660 nm light radiation, showing a good photodynamic therapy (PDT)/ chemotherapy (CT) synergistic effect. In addition, CABP showed excellent antibacterial and wound healing effects on S. aureus infection in a full-layer skin defect experiment. In short, the patch system is simple to prepare and easy to use, and can provide important research value for the integrated diagnosis and treatment system in biomedical applications.

Kopsileuconines A-D: Bisindole alkaloids with cytotoxic activity from Kopsia hainanensis.

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

Correlations between Immunoinflammatory Factor Levels and Cognitive Functions and Brain Structural Magnetic Resonance Imaging Features among Patients with Primary Schizophrenia.

BACKGROUND: Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Based on the latest concept of cognition, immunoinflammatory factors and structural magnetic resonance imaging (sMRI) features of the brain are considered markers of schizophrenia. This study explored the correlations between cognitive function and immunoinflammatory factors and sMRI in primary schizophrenia patients. METHODS: Non-interventional cross-sectional study was conducted, including 21 patients with primary schizophrenia, who were identified based on the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) and grouped under the observation group. Thirty healthy volunteers with age, gender, hand dominance, and education duration matched with those of the primary schizophrenia patients were recruited to the control group. All subjects underwent sMRI examination. MATRICS consensus cognitive battery (MCCB) was employed to assess the cognitive functions among patients with primary schizophrenia. The levels of serum amyloid A (SAA), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40) were measured by means of enzyme-linked immunosorbent assay (ELISA). Pearson's correlation analysis was carried out to analyze the correlation between immunoinflammatory factor levels and cognitive functions as well as brain sMRI features. RESULTS: The scores for all MCCB items and the total score for the observation group were apparently lower than those for the control group (p < 0.001), while the YKL-40 and SAA levels were notably higher in the observation group (t = 3.406, p < 0.05; t = 5.656, p < 0.001). Compared to the control group, the observation group exhibited reduced volumes of left and right insular lobes, left and right anterior cingulate cortexes, left and right hippocampi, right parahippocampal gyrus, right amygdala, left inferior occipital lobe, left superior temporal lobe, left temporal pole, and left middle and inferior temporal lobes (p < 0.001). The levels of YKL-40 and SAA were both negatively correlated with MCCB score (r = -0.3668, p = 0.004; r = -0.8495, p < 0.001). The volumes of right insular lobe, left and right anterior cingulate cortexes, right parahippocampal gyrus, right amygdala, and gray matter in left middle temporal lobe were all negatively correlated with the levels of YKL-40 and SAA (p < 0.05). CONCLUSION: Cognitive impairment in patients with primary schizophrenia is associated with increased serum SAA and YKL-40 levels and decreased gray matter volume.

MDH2 regulates the sensitivity of clear cell renal cell carcinoma to ferroptosis through its interaction with FSP1.

Malate dehydrogenase 2 is a pivotal enzyme in the tricarboxylic acid cycle. Recent studies have highlighted the significant involvement of MDH2 in the pathogenesis and progression of diverse types of tumors, yet its precise mechanistic underpinnings remain elusive. This study revealed a significant decrease in MDH2 expression in renal cancer tissues. And knocking out MDH2 was observed to hinder the proliferation of normal renal tubular epithelial cells but notably enhance the proliferation of ccRCC. Furthermore, mechanistically, we found that MDH2 inhibits the proliferation of ccRCC by promoting ferroptosis, while enhancing the sensitivity of ccRCC to ferroptosis inducers, promoting lipid peroxidation. We also demonstrated that MDH2 regulates the ubiquitination of FSP1 through protein-protein interactions, leading to a decrease in FSP1 protein levels and maintaining high sensitivity of ccRCC to ferroptosis. In conclusion, our study demonstrates that the reduced MDH2 expression in ccRCC results in increased expression of FSP1, thereby reducing its sensitivity to ferroptosis. It unveils a non-metabolic role for the downregulation of MDH2 in ccRCC progression.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

The modification role and tumor association with a methyltransferase: KMT2C.

Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges.

Feasibility of a novel unassisted single-channel transcolonic endoscopic appendectomy for the treatment of appendiceal lesions (with video).

BACKGROUND: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. METHOD: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure­related parameters, and follow­up data and analyzed the impact of previous abdominal surgery and traction technique. RESULTS: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3-15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. CONCLUSION: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases.