Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis.

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery.

A bio-based durable reactive flame retardant for cotton fabric based on lentinan.

Cotton fabric has extensive application due to its comfort and breathability. However, the inherent flammability limits its wide application. Durable polysaccharide-based flame retardants with a low impact on the softness of fabrics are rarely reported. In this work, a novel flame retardant ammonium phosphate of lentinan (APLNT) was synthesized and grafted on the surface of cotton fabric. The treated cotton fabric had a high limiting oxygen index (LOI) value of 43.3 % and passed the vertical burning test (VBT) with a 21.1 % weight gain of APLNT. Compared with control cotton, the peak heat release rate and total heat release values of Cotton-APLNT2 decreased by 92.8 % and 50.9 %, respectively. In addition, the cotton fabric still passed the VBT and kept an LOI value of 27.0 % even after 50 laundering cycles, indicating that the fabric can be used for daily needs. More importantly, the treated fabric remains soft. This research provided a new strategy for preparing bio-based durable flame retardant cotton fabrics.

KEMoS: A knowledge-enhanced multi-modal summarizing framework for Chinese online meetings.

The demand for "online meetings" and "collaborative office work" keeps surging recently, producing an abundant amount of relevant data. How to provide participants with accurate and fast summarizing service has attracted extensive attention. Existing meeting summarizing models overlook the utilization of multi-modal information and the information offsetting during summarizing. In this paper, we develop a knowledge-enhanced multi-modal summarizing framework. Firstly, we construct a three-layer multi-modal meeting knowledge graph, including basic, knowledge, and multi-modal layer, to integrate meeting information thoroughly. Then, we raise a topic-based hierarchical clustering approach, which considers information entropy and difference simultaneously, to capture the semantic evolution of meetings. Next, we devise a multi-modal enhanced encoding strategy, including a sentence-level cross-modal encoder, a joint loss function, and a knowledge graph embedding module, to learn the meeting and topic-level presentations. Finally, when generating summaries, we design a topic-enhanced decoding strategy for the Transformer decoder which mitigates semantic offsetting with the aid of topic information. Extensive experiments show that our proposed work consistently outperforms state-of-the-art solutions on the Chinese meeting dataset, where the ROUGE-1, ROUGE-2, and ROUGE-L are 49.98%, 21.03%, and 32.03% respectively.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Continuous quality improvement project to reduce the downtime of medical linear accelerators: A case study at Zhejiang Cancer Hospital.

Objective: To analyse and continually improve existing issues in the quality improvement process of medical linear accelerators (LINACs) and enhance the quality control management of LINACs. Methods: Data were collected from eight LINACs (sourced from three manufacturers) at Zhejiang Cancer Hospital using Excel diaries between January 2019 and December 2020. The data description and analysis were performed using the analytic hierarchy process, SPSSAU and Excel software, and mean-time-to-repair (MTTR)/mean-time-between-failure (MTBF) metrics. Continuous quality improvement was executed using the quality control circle (QCC) quality management method. Results: After quality improvement, the risk frequency of 'LINAC down' events decreased by 43.63% and downtime was reduced by 40.45%. The weight of downtime risk improved by 73.69%. The MTTR recovery value increased by 31.90%, and MTBF reliability increased by 2.97 h. The simulation results demonstrated that the proposed quality improvement measures could effectively decrease the frequency and duration of downtimes, consequently extending the normal operational time of LINACs. Conclusion: Transitioning from instant repair to preventative maintenance can enhance the operational efficiency of equipment and yield economic benefits for hospitals. The QCC method and the event risk evaluation model are effective in reducing the downtime of LINACs and improving their quality control management.

Machine learning models reveal the critical role of nighttime systolic blood pressure in predicting functional outcome for acute ischemic stroke after endovascular thrombectomy.

Background: Blood pressure (BP) is a key factor for the clinical outcomes of acute ischemic stroke (AIS) receiving endovascular thrombectomy (EVT). However, the effect of the circadian pattern of BP on functional outcome is unclear. Methods: This multicenter, retrospective, observational study was conducted from 2016 to 2023 at three hospitals in China (ChiCTR2300077202). A total of 407 patients who underwent endovascular thrombectomy (EVT) and continuous 24-h BP monitoring were included. Two hundred forty-one cases from Beijing Hospital were allocated to the development group, while 166 cases from Peking University Shenzhen Hospital and Hainan General Hospital were used for external validation. Postoperative systolic BP (SBP) included daytime SBP, nighttime SBP, and 24-h average SBP. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), Boruta were used to screen for potential features associated with functional dependence defined as 3-month modified Rankin scale (mRS) score ≥ 3. Nine algorithms were applied for model construction and evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Three hundred twenty-eight of 407 (80.6%) patients achieved successful recanalization and 182 patients (44.7%) were functional independent. NIHSS at onset, modified cerebral infarction thrombolysis grade, atrial fibrillation, coronary atherosclerotic heart disease, hypertension were identified as prognostic factors by the intersection of three algorithms to construct the baseline model. Compared to daytime SBP and 24-h SBP models, the AUC of baseline + nighttime SBP showed the highest AUC in all algorithms. The XGboost model performed the best among all the algorithms. ROC results showed an AUC of 0.841 in the development set and an AUC of 0.752 in the validation set for the baseline plus nighttime SBP model, with a brier score of 0.198. Conclusion: This study firstly explored the association between circadian BP patterns with functional outcome for AIS. Nighttime SBP may provide more clinical information regarding the prognosis of patients with AIS after EVT.

Recent advances in cotton fabric-based photocatalytic composites for the degradation of organic contaminants.

Cotton is one of the oldest and most widely used natural fibers in the world. It enables a wide range of applications due to its excellent moisture absorption, thermal insulation, heat resistance, and durability. Benefiting from current developments in textile technology and materials science, people are constantly seeking more comfortable, more beautiful and more versatile cotton fabrics. As the second skin of body, clothing not only provides the basic needs of wear but also increases the protection of body against different environmental stimuli. In this article, a comprehensive review is proposed regarding research activities of systematically summarise the development and research of cotton fabric-based photocatalytic composites for the degradation of organic contaminants in the area of self-cleaning, degradation of gaseous contaminants, pathogenic bacteria or viruses, and chemical warfare agents. Specifically, we begin with a brief exposition of the background and significance of cotton fabric-based photocatalytic composites. Next, a systematical review on cotton fabric-based photocatalytic composites is provided according to their mechanisms and advanced applications. Finally, a simple summary and analysis concludes the current limitations and future directions in these composites for the degradation of organic contaminants.

MedChatZH: A tuning LLM for traditional Chinese medicine consultations.

Generative Large Language Models (LLMs) have achieved significant success in various natural language processing tasks, including Question-Answering (QA) and dialogue systems. However, most models are trained on English data and lack strong generalization in providing answers in Chinese. This limitation is especially evident in specialized domains like traditional Chinese medical QA, where performance suffers due to the absence of fine-tuning and high-quality datasets. To address this, we introduce MedChatZH, a dialogue model optimized for Chinese medical QA based on transformer decoder with LLaMA architecture. Continued pre-training on a curated corpus of Chinese medical books is followed by fine-tuning with a carefully selected medical instruction dataset, resulting in MedChatZH outperforming several Chinese dialogue baselines on a real-world medical dialogue dataset. Our model, code, and dataset are publicly available on GitHub (https://github.com/tyang816/MedChatZH) to encourage further research in traditional Chinese medicine and LLMs.

Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Variability of bile bacterial profiles and drug resistance in patients with choledocholithiasis combined with biliary tract infection: a retrospective study.

Background: Biliary tract infection is a common complication of choledocholithiasis. This study aimed to analyse the distribution of pathogenic bacteria in bile cultures from patients with choledocholithiasis combined with biliary tract infection to guide clinical application of antimicrobials and reduce the emergence of drug resistance. Methods: A total of 880 patients were enrolled in this retrospective study from 30 March 2017 to 31 August 2022 at the Affiliated Hospital of Qingdao University in China. Bile specimens were extracted for microbiological culture under aseptic conditions using endoscopic retrograde cholangiopancreatography. Bacterial culture, strain identification, and antimicrobial susceptibility testing were conducted according to the standard protocol. Baseline data were retrieved from patient files. Results: Overall, 90.34% (795/880) of bile samples showed positive microbiological results and 37.50% (330/880) demonstrated polymicrobial infections. Among the 795 bile specimens with positive culture results, 1,216 pathogenic bacteria were detected, with gram-negative bacilli accounting for 56.33%, gram-positive cocci for 41.86%, and fungi for 1.81%. The predominant gram-negative bacilli in the bile cultures were Escherichia coli (30.43%) and Klebsiella pneumoniae (13.98%), whereas the main gram-positive cocci were Enterococcus faecium (14.04%) and E. casseliflavus (4.28%). The annual trend analysis revealed a gradual decrease in the proportion of gram-negative bacilli and a gradual increase in the proportion of gram-positive cocci, with a concomitant decrease in the dominance of E. coli. Both E. faecium and E. coli showed high resistance to conventional antibiotics but high sensitivity to piperacillin/tazobactam, carbapenems, amikacin, and vancomycin. Conclusions: A significant change has occurred in the bile bacterial spectrum in patients with choledocholithiasis and biliary tract infection. The incidence of gram-positive cocci infections has increased annually, while that of gram-negative bacilli and E. coli infections has decreased. Antibiotic administration should be tailored based on the local bacterial profile.

A role for the cerebellum in motor-triggered alleviation of anxiety.

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

A custom next-generation sequencing panel for 1p/19q codeletion and mutational analysis in gliomas.

The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffin-embedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time.

Identification of potential biomarkers and therapeutic targets related to post-traumatic stress disorder due to traumatic brain injury.

BACKGROUND: Post-traumatic stress disorder (PTSD), a disease state that has an unclear pathogenesis, imposes a substantial burden on individuals and society. Traumatic brain injury (TBI) is one of the most significant triggers of PTSD. Identifying biomarkers associated with TBI-related PTSD will help researchers to uncover the underlying mechanism that drives disease development. Furthermore, it remains to be confirmed whether different types of traumas share a common mechanism of action. METHODS: For this study, we screened the eligible data sets from the Gene Expression Omnibus (GEO) database, obtained differentially expressed genes (DEGs) through analysis, conducted functional enrichment analysis on the DEGs in order to understand their molecular mechanisms, constructed a PPI network, used various algorithms to obtain hub genes, and finally evaluated, validated, and analyzed the diagnostic performance of the hub genes. RESULTS: A total of 430 upregulated and 992 down-regulated differentially expressed genes were extracted from the TBI data set. A total of 1919 upregulated and 851 down-regulated differentially expressed genes were extracted from the PTSD data set. Functional enrichment analysis revealed that the differentially expressed genes had biological functions linked to molecular regulation, cell signaling transduction, cell metabolic regulation, and immune response. After constructing a PPI network and introducing algorithm analysis, the upregulated hub genes were identified as VNN1, SERPINB2, and ETFDH, and the down-regulated hub genes were identified as FLT3LG, DYRK1A, DCN, and FKBP8. In addition, by comparing the data with patients with other types of trauma, it was revealed that PTSD showed different molecular processes that are under the influence of different trauma characteristics and responses. CONCLUSIONS: By exploring the role of different types of traumas during the pathogenesis of PTSD, its possible molecular mechanisms have been revealed, providing vital information for understanding the complex pathways associated with TBI-related PTSD. The data in this study has important implications for the design and development of new diagnostic and therapeutic methods needed to treat and manage PTSD.

[Variation Characteristics of PM2.5 Pollution and Transport in Typical Transport Channel Cities in Winter].

Taking Handan, Xingtai, Hengshui, and Cangzhou, four cities in southwest Hebei Province along the Beijing-Tianjin-Hebei typical transport route, as examples, we analyzed the variation characteristics of 3a meteorological conditions and PM2.5 concentration in winter from 2019 to 2021 and used potential source contribution analysis (PSCF) and concentration weight analysis (CWT) to identify the transport characteristics of PM2.5 in the four cities during the study period. Based on the meteorological air quality model (WRF-CMAQ) transmission matrix method and transport flux method, the contribution of PM2.5 transport between Handan, Xingtai, Hengshui, and Cangzhou and the surrounding areas was quantitatively assessed; the vertical distribution characteristics of PM2.5 net transport flux were revealed; and the two main transport routes of PM2.5 pollution were further identified. The results showed that during the study period, the PM2.5 concentration decreased by 45.85%, 49.45%, 42.40%, and 31.65%, respectively. The potential source contribution of Handan and Xingtai was mainly distributed in south-central Shanxi (Linfen, Changzhi, and Jinzhong), northern Henan (Xinxiang, Kaifeng, and Zhengzhou), and a small part of Inner Mongolia (PSCF > 0.9). The potential contribution areas of Hengshui and Cangzhou were mainly concentrated in southern Hebei (Handan and Shijiazhuang), central Shanxi (Taiyuan and Yangquan), and some Shandong regions (PSCF > 0.7), and the CWT results were similar to those of PSCF. During the study period, the local contribution (51.11%-62.99%) was slightly higher than the regional contribution (37.01%-48.89%) during winter in the four cities. Affected by horizontal turbulence and vertical diffusion, the impact of regional transmission in 2020 was slightly higher than that in other years (0.50%-9.52%). In 2021, the influence of regional transmission was slightly lower than that of other years (-2.15%--9.52%) due to low PM2.5 concentration and meteorological factors. For Handan, Xingtai, Hengshui, and Cangzhou, the total inflow (outflow) flux intensity of the four cities during winter and the surrounding areas was in 2020 > 2021 > 2019. For the total net flux, the total inflow (outflow) flux intensity of the four cities in winter was 0.094, -0.070, and 0.087 kt·d-1 (Xingtai:0.212, 0.395, and 0.544 kt·d-1; Hengshui:-0.040, -0.228, and 0.185 kt·d-1; Cangzhou:0.062, 0.126, and 0.128 kt·d-1). During the study, Handan, Xingtai, and Cangzhou were mostly used as transport receptors, whereas Hengshui was mostly used as a transport source. In the range of 0-1 260 m, the net transport flux intensity of PM2.5 increased basically with the increase in height, and the maximum net flux of the various cities in different periods was different. The maximum net flux of Handan, Xingtai, and Hengshui was 252-1 261 m, 817 m, and 252-817 m, respectively. The maximum net flux in Cangzhou was 252-359 m. By analyzing the transmission characteristics of the four cities, it was found that there were two main transport directions of PM2.5, that is, the northwest-southeast direction (Shanxi → Handan → Henan and Shandong; Shijiazhuang → Xingtai → Handan and Shandong; Baoding → Cangzhou → Shandong) and the southwest-northeast direction (Shanxi → Xingtai → Hengshui → Cangzhou → Bohai Bay).

A universal eco-friendly flame retardant strategy for polylactic acid fabrics and other polymer substrates.

Various polymer substrates have their particular combustion features, therefore, developing an effective universal flame retardant strategy for various polymer substrates is of great practical importance. Meanwhile, as substitutes for petroleum-based products, bio-based flame retardants and biodegradable polylactic acid (PLA) meet the requirements of sustainable development. In this work, a fully bio-based flame retardant coating (PAGS) was prepared using phytic acid (PA) and guanosine (GS). PAGS was used as a universal flame retardant coatings for polylactic acid (PLA) fabrics and other substrates, including cotton fabrics, polyethylene terephthalate (PET) fabrics, polyamide (PA) fabrics, polyurethane (PU) foams, polyethylene terephthalate (PET) films, and woods. The PAGS-treated substrates were able to self-extinguish and eliminate molten droplets. Similarly, the PAGS coating significantly suppressed the heat release of each substrate. The P-containing free radicals in the gas phase were able to interact with highly reactive H, HO and alkyl radicals, blocking the chain reaction during combustion. The flammable gas density was also diluted by nonflammable gases. The formed continuous porous and dense intumescent char layer hindered heat and oxygen. It is suggested that this work provides a simple and efficient flame retardant strategy for improving the fire safety of various polymer substrates.

SH3RF2 contributes to cisplatin resistance in ovarian cancer cells by promoting RBPMS degradation.

Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance.

Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury.

PURPOSE: Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis. METHODS: Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization. RESULTS: Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. CONCLUSION: This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.