Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea.

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.

Discovery of novel melatonin-mydroxyquinoline hybrids as multitarget strategies for Alzheimer's disease therapy.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects human health, and current treatment strategies are far from meeting clinical needs. Inspired by multi-target drug design strategies, a series of novel natural products-based melatonin-hydroxyquinoline hybrids were designed and synthesized, targeting anti-oxidation and metal-chelating at the same time. Most of the compounds showed significant oxygen radical absorbance capacity and Aß1-42 aggregation inhibition. Moreover, the compounds possess good blood-brain barrier permeability. 6b and 6c have a good ability to alleviate oxidative stress induced by hydrogen peroxide. 6b and 6c possess metal-chelating properties with the chelation ratio being 2:1. Furthermore, 6b can significantly mitigate metal-induced Aß aggregation. This work may provide a new multi-target treatment strategy for Alzheimer's disease.

Retrospective Investigation and Research on Fall Events Among Hospitalized Patients in the Rehabilitation Department.

Objective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients. Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann-Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses. Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.-12:00 p.m. and 3:01 p.m.-6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40-60. Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.

Mutation characteristics and molecular evolution of ovarian metastasis from gastric cancer and potential biomarkers for paclitaxel treatment.

Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo.

Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Introduction: Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. Material and methods: This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. Results: The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). Conclusions: The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

Two Short-Wave UV Beryllium Selenites Exhibiting Diverse Optical Properties Stemming from Functional Group Arrangements.

The arrangement of functional groups exerts a crucial role in determining the characteristics of compounds. In this study, we synthesized two novel short-wave ultraviolet (UV) nonlinear optical (NLO) crystals: KBe2(SeO3)2(OH)·H2O and K2Be(SeO3)2. Interestingly, the two compounds show the same SeO3 triangular pyramids and K-O polyhedra. However, the two compounds exhibit distinct beryllium-oxygen anion groups: BeO3(OH) for KBe2(SeO3)2(OH)·H2O and BeO4 for K2Be(SeO3)2. This results in the SeO3 groups within the structure having different orientations, ultimately leading to the two compounds exhibiting completely different optical properties. KBe2(SeO3)2(OH)·H2O displays a large second harmonic generation (SHG) effect equivalent to 2× KH2PO4 (KDP), coupled with a large birefringence of 0.078 at 546 nm. In contrast, the SHG effect and birefringence of K2Be(SeO3)2 are only 0.33× that of KDP and 0.024 at 546 nm, respectively. Structural analyses and theoretical calculations indicate that these pronounced differences in optical properties stem from variations in the arrangement of the SeO3 functional groups. This study not only sheds light on the correlation between crystal structure and optical behavior but also presents a hopeful avenue for the advancement of materials in the short-wave UV spectrum.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

Recombinant manufacturing of multispecies biolubricants.

Lubricin, a lubricating glycoprotein abundant in synovial fluid, forms a low-friction brush polymer interface in tissues exposed to sliding motion including joints, tendon sheaths, and the surface of the eye. Despite its therapeutic potential in diseases such as osteoarthritis and dry eye disease, there are few sources available. Through rational design, we developed a series of recombinant lubricin analogs that utilize the species-specific tissue-binding domains at the N- and C-termini to increase biocompatibility while replacing the central mucin domain with an engineered variant that retains the lubricating properties of native lubricin. In this study, we demonstrate the tissue binding capacity of our engineered lubricin product and its retention in the joint space of rats. Next, we present a new bioprocess chain that utilizes a human-derived cell line to produce O-glycosylation consistent with that of native lubricin and a purification strategy that capitalizes on the positively charged, hydrophobic N- and C-terminal domains. The bioprocess chain is demonstrated at 10 L scale in industry-standard equipment utilizing commonly available ion exchange, hydrophobic interaction and size exclusion chromatography resins. Finally, we confirmed the purity and lubricating properties of the recombinant biolubricant. The biomolecular engineering and bioprocessing strategies presented here are an effective means of lubricin production and could have broad applications to the study of mucins in general.

Prevalence and bidirectional association of sleep quality and gut health among Chinese midwives: a large population, multi-center cross-sectional study.

Background: Shift work can disrupt sleep quality and gut health. Nurses and midwives constitute approximately half of the global healthcare shift-working workforce. Our previous study revealed that most midwives were experiencing suboptimal health conditions, characterized by poor sleep quality and a high prevalence of gastrointestinal diseases. The gut-brain axis theory highlights the potential interplay between sleep quality and gut health. However, limited research focuses on this relationship among midwives. Methods: A cross-sectional survey included 2041 midwives from 87 Chinese hospitals between March and October 2023. Participants completed standardized questionnaires assessing sleep quality, gut health, depression, anxiety, and work stress. Binary logistic regression analyzed factors associated with poor sleep, and multiple linear regression examined the influence of sleep quality on gut health. Results: Over 60% of midwives reported poor sleep, with many experiencing gastrointestinal disorders. We observed a bidirectional relationship between sleep quality and gut health among midwives. After multivariable adjustments, midwives with higher gut health scores were more likely to experience poor sleep quality (odds ratio = 1.042, 95% confidence interval = 1.03-1.054). Conversely, midwives with higher sleep quality scores were also more likely to have poor gut health (ß = 0.222, 95% confidence interval = 0.529-0.797). These associations remained robust across sensitivity analyses. Furthermore, depression, anxiety, and work stress significantly affected both sleep quality and gut health among midwives. Conclusion: This study enhances our understanding of the intricate relationship between sleep quality and gut health among midwives. Poor gut health was associated with a higher risk of poor sleep, and vice versa. To improve the overall wellbeing of midwives, the findings emphasize the importance of addressing poor sleep quality and promoting gut health through maintaining a healthy diet, lifestyle, and good mental health. Further studies are needed to confirm our findings and clarify the underlying mechanisms.

Turn-off enzyme activity of histidine-rich peptides for the detection of lysozyme.

An assay that integrates histidine-rich peptides (HisRPs) with high-affinity aptamers was developed enabling the specific and sensitive determination of the target lysozyme. The enzyme-like activity of HisRP is inhibited by its interaction with a target recognized by an aptamer. In the presence of the target, lysozyme molecules progressively assemble on the surface of HisRP in a concentration-dependent manner, resulting in the gradual suppression of enzyme-like activity. This inhibition of HisRP's enzyme-like activity can be visually observed through color changes in the reaction product or quantified using UV-visible absorption spectroscopy. Under optimal conditions, the proposed colorimetric assay for lysozyme had a detection limit as low as 1 nM and exhibited excellent selectivity against other nonspecific interferents. Furthermore, subsequent research validated the practical applicability of the developed colorimetric approach to saliva samples, indicating that the assay holds significant potential for the detection of lysozymes in samples derived from humans.

The larva and adult of Helicoverpa armigera use differential gustatory receptors to sense sucrose.

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100-1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.

Effectiveness of Early Multimodal Non-pharmacological Interventions in Cognitive Preservation in the Elderly.

INTRODUCTION: Multimodal non-pharmacological interventions (MNPI) have been determined as effective in delaying cognitive deterioration. The effectiveness of timing of such interventions in elderly is less discussed. We compared the different effectiveness of MNPI in cognitive preservation in elderly subjects with and without dementia. METHODS: We enrolled volunteer the elderly subjects. Subjects were classified as dementia group and non-dementia group by instrument of ascertainment of dementia 8. All were assigned to attend 3 hours of MNPI (physical fitness training, Chinese capillary, and Chinese drawings and paintings) twice a week over a 16-week period. Neuropsychiatric tests, including Mini-Mental State Examination (MMSE), Cognitive Assessment Screening Instrument (CASI), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI), were administered before and 1 year after MNPI. We demonstrated the changes of cognition and behavioral and psychological symptoms of dementia (BPSD) before and after MNPI. We compared the different effectiveness of cognition preservation between two groups. RESULTS: In total, there were 43 participants in our study, including 18 with non-dementia and 25 with dementia. The non-dementia group had a significantly higher proportion of cognitive preservation in remote memory (100.0% vs 68.0%, P = .007), orientation (94.4% vs 48.0%, P = .001), drawing (94.4% vs 64.0%, P = .021) and language (77.8% vs 48.0%, P = .049) than the dementia group. The highest proportion of preserved cognition after MNPI was remote memory (100%), followed by orientation (94.4%) and drawing (94.4%) in the non-dementia group. The highest proportion of preserved cognition after MNPI was attention (72%) followed by remote memory (68%), recent memory (64%) and drawing (64%) in the dementia group. Overall, their improved rate in behavioral and psychological symptoms was 55.6%. CONCLUSION: Our study concluded the benefits of early MNPI in cognition preservation in the elderly, especially in the field of remote memory, orientation, drawing and language.

Pharmacological Research Progress of Novel Antihypertensive Drugs.

Cardiovascular disease stands as the leading cause of death globally, with hypertension emerging as an independent risk factor for its development. The worldwide prevalence of hypertension hovers around 30%, encompassing a staggering 1.2 billion patients, and continues to escalate annually. Medication plays a pivotal role in managing hypertension, not only effectively regulating blood pressure (BP) but also substantially mitigating the occurrence of cardiovascular and cerebrovascular diseases. This review comprehensively outlines the categories, mechanisms, clinical applications, and drawbacks of conventional antihypertensive drugs. It delves into the five primary pharmacological classifications, namely ß-receptor blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and diuretics. The emphasis is placed on elucidating the mechanisms, advantages, and research progress of novel antihypertensive drugs targeting emerging areas. These include mineralocorticoid receptor antagonists (MRAs), atrial natriuretic peptides (ANPs), neutral endopeptidase inhibitors (NEPIs), sodium-dependent glucose transporter 2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), endothelin receptor antagonists (ERAs), soluble guanylate cyclase (sGC) agonists, brain aminopeptidase A inhibitors (APAIs), and small interfering ribonucleic acids (siRNAs) targeting hepatic angiotensinogen. Compared to conventional antihypertensive drugs, these novel alternatives exhibit favorable antihypertensive effects with minimal adverse reactions. This review serves as a valuable reference for future research and the clinical application of antihypertensive drugs.

Two histidine-templated metal phosphate-oxalates: solvent-free synthesis, luminescence, and proton-conducting properties.

Two new histidine-templated metal phosphate-oxalates (MPOs) were prepared under solvent-free conditions. Single-crystal X-ray diffraction analysis reveals that they have layered and chainlike structures, respectively. Under ultraviolet light irradiation, the two MPOs exhibit blue luminescence originating from histidine templates. Their proton-conducting properties were also investigated under different conditions.

Cancer-derived exosomal lncRNA SNHG3 promotes the metastasis of colorectal cancer through hnRNPC-mediating RNA stability of ß-catenin.

Metastasis is the leading cause of death in colorectal cancer (CRC) patients. By mediating intercellular communication, exosomes exhibit considerable value in regulating tumor metastasis. Long non-coding RNAs (lncRNAs) are abundant in exosomes and participate in regulating tumor progression. However, it is poorly understood how the cancer-secreted exosomal lncRNAs affect CRC proliferation and metastasis. Here, by analyzing the public databases we identified a lncRNA SNHG3 and demonstrated that SNHG3 was delivered through CRC cells-derived exosomes to promote metastasis in CRC. Mechanistically, exosomal SNHG3 was internalized by CRC cells and afterward upregulated the expression of ß-catenin by facilitating the intranuclear transport of hnRNPC. Consequently, the RNA stability of ß-catenin was enhanced which led to the activation of EMT and metastasis of CRC cells. Our findings expand the oncogenic mechanisms of exosomal SNHG3 and identify it as a diagnostic marker for CRC.

Luminescence-Monitored Progressive Chemical Pressure Implementation Realized through Successive Y3+ and Mg2+ Doping into Ca10.5(PO4)7:Eu2.

Chemical pressure generated through ion doping into crystal lattices has been proven to be conducive to exploration of new matter, development of novel functionalities, and realization of unprecedented performances. However, studies are focusing on one-time doping, and there is a lack of both advanced investigations for multiple doping and sophisticated strategies to precisely and quantitatively track the gradual functionality evolution along with progressive chemical pressure implementation. Herein, high-valent Y3+ and equal-valent Mg2+ is successively doped to replace multiple Ca sites in Ca10.5(PO4)7:Eu2+. The luminescence evolution of Eu2+ serves as an optical probe, allowing step-by-step and atomic-level tracking of the site occupation of Y3+ and Mg2+, interassociation of Ca sites, and ultimately functionality improvement. The resulting Ca8MgY(PO4)7:Eu2+ displays a record-high relative sensitivity for optical thermometry. Utilization of the environment-sensitive emission of Eu2+ as a luminescent probe has offered a unique approach to monitoring structure-functionality evolution in vivo with atomic precision, which shall also be extended to optimization of other functionalities such as ferroelectricity, conductivity, thermoelectricity, and catalytic activity through precise control over atomic diffusion in other types of substances.

LncRNA MIR210HG promotes phenotype switching of pulmonary arterial smooth muscle cells through autophagy-dependent ferroptosis pathway.

Hypoxic pulmonary hypertension (HPH) is a pathophysiological syndrome in which pulmonary vascular pressure increases under hypoxic stimulation and there is an urgent need to develop emerging therapies for the treatment of HPH. LncRNA MIR210HG is a long non-coding RNA closely related to hypoxia and has been widely reported in a variety of tumor diseases. But its mechanism in hypoxic pulmonary hypertension is not clear. In this study, we identified for the first time the potential effect of MIR210HG on disease progression in HPH. Furthermore, we investigated the underlying mechanism through which elevated levels of MIR210HG promotes the transition from a contractile phenotype to a synthetic phenotype in PASMCs under hypoxia via activation of autophagy-dependent ferroptosis pathway. While overexpression of HIF-2α in PASMCs under hypoxia significantly reversed the phenotypic changes induced by MIR210HG knockdown. We further investigated the potential positive regulatory relationship between STAT3 and the transcription of MIR210HG in PASMCs under hypoxic conditions. In addition, we established both in vivo and in vitro models of HPH to validate the differential expression of specific markers associated with hypoxia. Our findings suggest a potential mechanism of LncRNA MIR210HG in the progression of HPH and offer potential targets for disease intervention and treatment.

Four and a half LIM domains 2 (FHL2) attenuates tumorigenesis of gastrointestinal stromal tumors (GISTs) by negatively regulating KIT signaling.

Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild-type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild-type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first-line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild-type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug-resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.

Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation, invasion, and migration of gastric cancer cells.

BACKGROUND: The precise role of mitochondrial carrier homolog 2 (MTCH2) in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated. AIM: To determine the role of MTCH2 in gastric cancer. METHODS: We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues, constructed MTCH2-overexpressing and MTCH2-knockdown cell models, and evaluated the proliferation, migration, and invasion of human gastric epithelial cells (GES-1) and human gastric cancer cells (AGS) cells. The mitochondrial membrane potential (MMP), mitochondrial permeability transformation pore (mPTP) and ATP fluorescence probe were used to detect mitochondrial function. Mitochondrial function and ATP synthase protein levels were detected via Western blotting. RESULTS: The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues. Overexpression of MTCH2 promoted colony formation, invasion, migration, MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis; knockdown of MTCH2 had the opposite effect, promoting overactivation of the mPTP and promoting apoptosis. CONCLUSION: MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation, invasion, and migration of gastric cancer cells by regulating mitochondrial function, providing a basis for targeted therapy for gastric cancer cells.

The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review.

Acute interstitial nephritis (AIN) is a significant contributor to acute kidney injury and can be attributed to a variety of factors, including but not limited to allergens or drugs, infections, autoimmune or systemic diseases, and idiopathic forms of the disease. In some cases, AIN requires a therapeutic action according to a single specific etiology by handling the offending agent and applying an immunosuppressant. Although AIN can be diagnosed through renal biopsy, it is not able to pinpoint the precise cause when multiple causes are suspected to be present simultaneously. Such situations arise when a patient suffering from infection develops AIN during antibiotic therapy, the exact causative factor of which becomes a challenge for the clinicians to determine. This is attributed to the different approaches employed in different etiologies, wherein clinicians are required to maintain the current antibiotic therapy or augment the dose in cases of infection as AIN etiology, without resorting to immunosuppressant therapy as the primary objective is infection killing. In contrast, antibiotics as an etiology for AIN require an alternative drug from the antibiotics group, along with an immunosuppressant. In the interim, delaying the identification of the precise cause may result in interstitial fibrosis and chronic kidney disease. This narrative review highlights certain findings that can be typical of infection-associated ATIN compared with antibiotic-associated ATIN based on clinical history and physical examination, clinical presentation of different antibiotic drug classes, histopathological features, classical and novel biomarkers, serum and urine cytokines and chemokines, cellular biomarkers, and genetic biomarkers. Although these findings cannot provide conclusive and clear recommendations that can be useful in the clinical practice, they can entice researchers to conduct original research on these features to discover clear recommendations.