[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Effects of extracorporeal diaphragm pacing combined with inspiratory muscle training on respiratory function in people with stroke: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of external diaphragmatic pacing (EDP) combined with inspiratory muscle training on respiratory function in post-stroke patients. METHODS: Patients with stroke were enrolled from the First Affiliated Hospital of Soochow University in China between 2021 and 2022. The patients were randomized into an EDP treatment group (control group) or an EDP treatment plus inspiratory muscle training group (experimental group). Each therapy was administered once a day for 6 days per week. The peak inspiratory flow (PIF), maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% ratio, and diaphragm thickness and mobility were measured and compared between the two groups after 4 weeks. RESULTS: After 4 weeks of intervention, respiratory muscle function indicators including PIF (95% CI: 0.21-1.28, p = 0.008) and MIP (95% CI: 6.92-25.44, p = 0.001) significantly improved in the experimental group. Diaphragmatic thickness also significantly increased in the experimental group (p < 0.05), while diaphragmatic excursion showed no significant difference between the two groups. Additionally, FVC (95% CI: 0.14-1.14, p = 0.013) and FEV1 (95% CI: 0.20-1.06, p = 0.005) demonstrated a significant increase in the experimental group, whereas FEV1/FVC% (95% CI: -0.84 to 9.36, p = 0.099) exhibited no significant group difference. CONCLUSION: EDP combined with inspiratory muscle training in individuals with stroke provides greater benefits than EDP alone in terms of respiratory function recovery, except for the parameters of diaphragmatic excursion and FEV1/FVC%.

Alkaloid-metabolites from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Nine metabolites, including three undescribed alkaloids pyripyropenes VW (1-2), penicioxa A (4), two previously reported pyripyropene A (3), oxaline (5), three grisephenone-type xanthone derivatives (6-8), and a diphenyl ether derivative 4-chloro-7,4'-dihydroxy-5,2'-dimethoxy-2-methylformate-6'-methybenzophone (9), were isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. Their structures were determined by spectroscopic analysis, ECD calculations, together with DP4+ probability analysis. Furthermore, all the isolated compounds were tested for cytotoxicity and anti-phytopathogenic fungal activities. Compounds 6-8 showed moderate cytotoxicity against tumor cell lines A549, with IC50 values ranging from 5.68 ± 0.21 to 9.71 ± 0.34 µg/mL, respectively.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KRP (KIP-RELATED PROTEIN) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with SHOOT MERISTEMLESS (STM), which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Advances and future perspectives of intranasal drug delivery: A scientometric review.

Intranasal drug delivery is as a noninvasive and efficient approach extensively utilized for treating the local, central nervous system, and systemic diseases. Despite numerous reviews delving into the application of intranasal drug delivery across biomedical fields, a comprehensive analysis of advancements and future perspectives remains elusive. This review elucidates the research progress of intranasal drug delivery through a scientometric analysis. It scrutinizes several challenges to bolster research in this domain, encompassing a thorough exploration of entry and elimination mechanisms specific to intranasal delivery, the identification of drugs compatible with the nasal cavity, the selection of dosage forms to surmount limited drug-loading capacity and poor solubility, and the identification of diseases amenable to the intranasal delivery strategy. Overall, this review furnishes a perspective aimed at galvanizing future research and development concerning intranasal drug delivery.

Inhibiting the m6A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown. Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition. Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression. Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

Characterization of Fe-Containing and Pb-Containing Nanoparticles Resulting from Corrosion of Plumbing Materials in Tap Water Using a Hyphenated ATM-DMA-spICP-MS System.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used to characterize metallic nanoparticles (NPs) assuming that all NPs are spherical and composed of pure element. However, environmental NPs generally do not meet these criteria, suggesting that spICP-MS may underestimate their true sizes. This study employed a system hyphenating the atomizer (ATM), differential mobility analyzer (DMA), and spICP-MS to characterize metallic NPs in tap water. Its performance was validated by using reference Au nanoparticles (AuNPs) and Ag-shelled AuNPs. The hyphenated system can determine the actual size and metal composition of both NPs with additional heating after ATM, while stand-alone spICP-MS misidentified the Ag-shelled AuNPs as smaller individual AgNPs and AuNPs. Dissolved metal ions could introduce artifact NPs after heating but could be eliminated by centrifugation. The hyphenated system was applied to characterize Fe-containing and Pb-containing NPs resulting from the corrosion of plumbing materials in tap water. The mode sizes of Fe-containing and Pb-containing NPs were determined to be 110 and 100 nm and the particle number concentrations were determined to be 4.99 × 107 and 1.40 × 106 #/mL, respectively. Cautions should be paid to potential changes in particle size induced by heating for metallic NPs with a low melting point or a high organic content.

Ethanol extract of Verbena officinalis alleviates MCAO-induced ischaemic stroke by inhibiting IL17A pathway-regulated neuroinflammation.

BACKGROUND: The prevention and treatment of ischaemic stroke is a worldwide challenge, and effective clinical treatment strategies are lacking. Studies have demonstrated the efficacy of Verbena officinalis in managing cerebrovascular disorders. However, the neuroprotective bioactive components and mechanisms remain unclear. PURPOSE: To investigate the pharmacological combinatorial components and mechanism underlying the anti-ischemic stroke effect of the ethanol extract of Verbena officinalis (VO Ex). STUDY DESIGN AND METHODS: The components of VO Ex were identified by HPLC. A middle cerebral artery occlusion (MCAO) induced brain injury model was used to assess the therapeutic effect of VO Ex. The activity of the chemical components of VO Ex was evaluated using a primary astrocyte injury model induced by oxygen-glucose deprivation/reperfusion (OGD/R). RNA sequencing was used to reveal the potential targets of VO Ex against cerebral ischemia-reperfusion injury (CIRI), and the results were verified by qRT-PCR and western blotting. The key components and target binding ability were predicted by molecular docking. Finally, the mechanism of combinatorial components was verified by experiments. RESULTS: The HPLC results indicated that the main ingredients of VO Ex were hastatoside, verbenalin, acteoside, luteolin, apigenin and hispidulin. In vivo experiments showed that VO Ex improved MCAO-induced acute cerebral ischemic injury. Transcriptomic data and biological experiments suggested that VO Ex exerted therapeutic effects through IL17A signalling pathways. The in vitro experiments indicated that verbenalin, acteoside, luteolin, apigenin and hispidulin exhibited neuroprotective activities. The novel formula of VALAH, derived from the aforementioned active ingredients, exhibited superior efficacy compared to each individual component. Molecular docking and mechanistic studies have confirmed that VALAH functions in the treatment of ischaemic stroke by suppressing the activation of the IL17A signalling pathway. CONCLUSION: This work is the first to reveal that VO Ex effectively inhibits the IL17A signaling pathway and mitigates neuroinflammation following ischemic stroke. Moreover, we identified the novel formula VALAH as the bioactive combinatorial components for VO Ex. Further research suggests that the activity of VALAH is associated with IL17A-mediated regulation of neuroinflammation. This finding provides new insights into the efficacious components and mechanisms of traditional Chinese medicine.

Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: Glycine dehydrogenase (GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). METHODS: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B (CHB), and 35 healthy controls (HCs). The methylation status of GLDC promoter in peripheral mononuclear cells (PBMCs) was identified by methylation specific polymerase chain reaction (MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction (qPCR). RESULTS: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients (27.0%) compared to that in CHB patients (68.6%) and HCs (74.3%) (P < 0.001). The methylated group had lower alanine aminotransferase level (P = 0.035) and lower rates of tumor node metastasis (TNM) III/IV (P = 0.043) and T3/T4 (P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients (P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters (P = 0.003). The diagnostic accuracy of alpha-fetoprotein (AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone (AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients (P = 0.038). CONCLUSIONS: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

A Wearable Assistant Device for the Hearing Impaired to Recognize Emergency Vehicle Sirens with Edge Computing.

Wearable assistant devices play an important role in daily life for people with disabilities. Those who have hearing impairments may face dangers while walking or driving on the road. The major danger is their inability to hear warning sounds from cars or ambulances. Thus, the aim of this study is to develop a wearable assistant device with edge computing, allowing the hearing impaired to recognize the warning sounds from vehicles on the road. An EfficientNet-based, fuzzy rank-based ensemble model was proposed to classify seven audio sounds, and it was embedded in an Arduino Nano 33 BLE Sense development board. The audio files were obtained from the CREMA-D dataset and the Large-Scale Audio dataset of emergency vehicle sirens on the road, with a total number of 8756 files. The seven audio sounds included four vocalizations and three sirens. The audio signal was converted into a spectrogram by using the short-time Fourier transform for feature extraction. When one of the three sirens was detected, the wearable assistant device presented alarms by vibrating and displaying messages on the OLED panel. The performances of the EfficientNet-based, fuzzy rank-based ensemble model in offline computing achieved an accuracy of 97.1%, precision of 97.79%, sensitivity of 96.8%, and specificity of 97.04%. In edge computing, the results comprised an accuracy of 95.2%, precision of 93.2%, sensitivity of 95.3%, and specificity of 95.1%. Thus, the proposed wearable assistant device has the potential benefit of helping the hearing impaired to avoid traffic accidents.

Targeting TRPV1 and TRPA1: A feasible strategy for natural herbal medicines to combat postoperative ileus.

Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

Intrathecal autologous thrombin-activated condensed platelet cytokines in chronic neurodegenerative disease: A hypothesis for anti-inflammatory and regenerative response.

Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and disordered neuronal signaling subsequently become cardinal features of Alzheimer's disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson's disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity. Importantly, both diagnoses feature hyperinflammation and intrathecal cytokine changes. Thus far, numerous clinical trials have produced nothing effective for AD or PD, yet the anti-inflammatory and regenerative potential of autologous platelet-rich plasma (PRP) remains largely unexamined in this context. Our report explores a proposed Phase I study on intrathecal condensed plasma growth factors processed from thrombin-activated PRP as monotherapy for AD or PD. The concept gains support from related work where cytokines of platelet origin successfully lowered inflammation, corrected background fibrosis, deactivated abnormal cells, and recovered local tissue function-all desirable outcomes in AD and PD. While PRP-mediated effects on membrane potentials, cellular signaling, electrolyte balance, and water clearance are less well characterized, experimental data suggest these pathways could likewise influence glymphatic drainage to ameliorate proteinopathies. As a well-tolerated 'orthobiologic' with no hypersensitivity risk, intrathecal PRP and its derivatives bring advantages over synthetic pharmaceuticals. If age-associated neuroinflammation in AD and PD is an upstream event inciting or contributing to neural disruption, then dampening local oxidative stress by a patient's own platelet cytokines (successful in other contexts) could offer therapeutic relevance to these neurodegenerative conditions as well.

A life-threatening bleeding prediction model for immune thrombocytopenia based on personalized machine learning: a nationwide prospective cohort study.

Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.

Sugar status in preexisting leaves determines systemic stomatal development within newly developing leaves.

Stomata are pores found in the epidermis of stems or leaves that modulate both plant gas exchange and water/nutrient uptake. The development and function of plant stomata are regulated by a diverse range of environmental cues. However, how carbohydrate status in preexisting leaves might determine systemic stomatal formation within newly developing leaves has remained obscure. The glucose (Glc) sensor HEXOKINASE1 (HXK1) has been reported to decrease the stability of an ethylene/Glc signaling transcriptional regulator, EIN3 (ETHYLENE INSENSITIVE3). EIN3 in turn directly represses the expression of SUC2 (sucrose transporter 2), encoding a master transporter of sucrose (Suc). Further, KIN10, a nuclear regulator involved in energy homeostasis, has been reported to repress the transcription factor SPCH (SPEECHLESS), a master regulator of stomatal development. Here, we demonstrate that the Glc status of preexisting leaves determines systemic stomatal development within newly developing leaves by the HXK1-¦EIN3-¦SUC2 module. Further, increasing Glc levels in preexisting leaves results in a HXK1-dependent decrease of EIN3 and increase of SUC2, triggering the perception, amplification and relay of HXK1-dependent Glc signaling and thereby triggering Suc transport from mature to newly developing leaves. The HXK1-¦EIN3-¦SUC2 molecular module thereby drives systemic Suc transport from preexisting leaves to newly developing leaves. Subsequently, increasing Suc levels within newly developing leaves promotes stomatal formation through the established KIN10⟶ SPCH module. Our findings thus show how a carbohydrate signal in preexisting leaves is sensed, amplified and relayed to determine the extent of systemic stomatal development within newly developing leaves.

Drimane-type sesquiterpenoids and their anti-inflammatory evaluation from Pyrrhoderma noxium HNNU0524.

Chemical investigation of a culture broth from the marine-derived fungus Pyrrhoderma noxium HNNU0524 yielded two new compounds including a drimane-type sesquiterpenoid named pyrrnoxin A (1) and a benzoic acid derivative, pyrrnoxin B (5), together with three related known analogues (2-4). The chemical structures of 1 and 5 were determined by detailed analysis of spectroscopic data, single-crystal X-ray crystallography, quantum mechanics-based DP4+ and ECD calculations. Compounds 2 and 3 moderately inhibited NO production of lipopolysaccharide-induced microglia cells BV2 with IC50 values of 26.6 and 60.5 µM, respectively.

Intracranial large artery embolism due to carotid thrombosis caused by a neck massager: A case report.

BACKGROUND: There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager. Herein we report such a case. CASE SUMMARY: A 49-year-old woman presented with left limb weakness and dysarthria after a history of neck massage for 1 mo. Neurological examination showed left central facial paralysis and left hemiparesis with a National Institutes of Health Stroke Scale score of 12. Brain magnetic resonance imaging revealed restricted diffusion on diffusion-weighted imaging in the right parietal and temporal lobes. Computed tomography angiography (CTA) indicated M3 segment embolism of the right middle cerebral artery. Neck CTA revealed thrombosis of the bilateral common carotid arteries. Carotid ultrasound showed thrombosis in the bilateral common carotid arteries (approximately 2 cm below the proximal end of the carotid sinus), and contrast-enhanced ultrasound did not suggest enhancement. No hypertension, diabetes, heart disease, vasculitis, or thrombophilia was found after admission. After 1 wk of treatment with aspirin 200 mg and atorvastatin 40 mg, a carotid ultrasound reexamination showed that the thrombosis had significantly reduced. CONCLUSION: Neck massager may cause carotid artery thrombosis.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.

Efficacy and safety of piperacillin-tazobactam compared with meropenem in treating complicated urinary tract infections including acute pyelonephritis due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

Introduction: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs. Methods: A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae. Results: Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01). Discussion: In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.