Cyclo(Pro-Tyr) elicits conserved cellular damage in fungi by targeting the [H+]ATPase Pma1 in plasma membrane domains.

Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes.

Hypertension and its association to phenotype on left ventricular function in hypertrophic cardiomyopathy patients assessed by cardiovascular magnetic resonance imaging.

AIM: The impact of hypertension (HT) on phenotypic expression in individuals with hypertrophic cardiomyopathy (HCM) is unclear. MATERIALS AND METHODS: Thirty-six HCM individuals without HT, 27 HCM with HT, and 20 age- and sex-matched healthy controls who underwent cardiovascular magnetic resonance imaging (CMR) to evaluate left ventricular (LV) function and strain were enrolled. Three groups' LV function and strain were compared. We also investigated whether HT was associated with reduced LV strain in HCM patients using univariate and multivariate linear regression analyses. RESULTS: HCM (with/without HT) patients had higher LV mass and LV mass index than the normal controls group. Furthermore, global radial strain, global circumferential strain (GCS), global longitudinal strain, global peak systolic strain rate of radial, and global peak diastolic strain rate of radial were significantly lower in HCM patients with HT, intermediate in HCM patients without HT, and greater in the normal controls (all, P<0.05). Worse GCS was observed in HCM patients with HT than those without HT (P<0.05). Multivariable linear regression analysis showed that HT was independently associated with impaired LV ejection fraction and reduced strain (all P<0.05). CONCLUSION: The presence of HT was associated with an adverse phenotype, including worse ejection fraction and reduced strains in HCM patients. In addition, management of HT and its effect on the clinical outcomes in HCM patients needs to be studied.

[The application and reflection of emerging molecular detection technologies in Salmonella detection].

Salmonella is an important foodborne pathogen and one of the main causes of diarrhea. Every year, about 550 million people suffer from diarrhea due to Salmonella infection, of which about 230 000 die. It has become a major global public safety issue. The application fields of Salmonella detection involve food safety, water quality monitoring, animal husbandry, public health monitoring, and medical diagnosis. The detection requirements mainly come from three aspects: pathogen identification, serotype identification, drug resistance and virulence identification. In recent years, the detection technology for Salmonella has made rapid progress, especially the emergence and development of emerging molecular detection technologies, providing new perspectives for Salmonella detection in different scenarios. However, due to the diversity of Salmonella serotypes and the complexity of detection scenarios, existing detection technologies still have some pain points (such as long detection time, cumbersome operation steps, low scene adaptability, etc.). This article will elaborate on the application of several emerging molecular detection technologies with distinct characteristics, such as CRISPR Cas technology, digital PCR technology, sequencing technology, and microfluidic technology, in Salmonella detection. It aims to provide a reference for the development and improvement of Salmonella detection technology and the establishment of infection warning and control systems.

[Feasibility and safety of remote programming in postoperative follow-up of cardiovascular implantable electronic devices].

Objective: To explore the feasibility and safety of remote programming technology based on 5G cloud technology support platform in postoperative follow-up of cardiovascular implantable electronic devices(CIED). Methods: This study was a multicenter cross-sectional study. CIED patients from 12 hospitals lacking full-time follow-up specialists in Sichuan Province were enrolled from June 2021 to October 2021. All patients' devices received remote inspecting and programming by the follow-up specialist of the remote follow-up center of the Third People's Hospital of Chengdu through 5G cloud technology support platform. The baseline data, device alarm events, device reprogramming events, adverse reactions and satisfaction questionnaire survey results were collected. Results: A total of 195 CIED implantation patients were included, with an age of (72.5±11.3) years, including 103 males (52.6%). All patients completed remote inspecting and programming successfully, with a duration of (5.8±4.0) min. Ninety-one patients' CIED were reprogrammed, with a total of 104 parameter adjustments. No abnormal communication or adverse events occurred. The satisfaction questionnaire showed that 97.9%(191/195) of the patients trusted or relatively trusted remote follow-up and 86.7%(169/195) of the patients were willing to choose remote follow-up mode for device management. Conclusion: The remote programming based on 5G cloud technology support platform may be feasible and safe for postoperative follow-up of CIED patients.

[Spinal endoscopic technique in the surgical treatment of thoracic ossification of the ligamentum flavum].

Thoracic ossification of the ligamentum flavum (TOLF) is a pathological heterotopic ossification disease in which the fibrous tissue of the ligamentum flavum of the thoracic spine converts into bony tissue, often leading to thoracic spinal stenosis and compression of the thoracic spinal cord nerve. When TOLF patients present with symptoms of spinal cord nerve compression, surgical treatment is usually required, and traditional open surgery is more invasive and carries a higher risk of spinal cord nerve injury. In recent years, domestic and foreign researchers have tried to apply spinal endoscopic techniques such as microendoscopy, percutaneous foraminoscopy, and unilateral biportal endoscopy for the treatment of TOLF, which can maximize the preservation of normal bone while achieving adequate decompression of the spinal cord nerve, with less damage to spinal stability, and have the advantages of less surgical trauma, less bleeding, and faster postoperative recovery. Due to the special anatomical structure of the thoracic vertebra, spinal endoscopic techniques should focus on safety and it is recommended that they are performed in experienced centers, and surgical indications should be strictly controlled.

Dexamethasone relieves the inflammatory response caused by inguinal hernia meshes through miR-155.

BACKGROUND: Inguinal hernia is a relatively common condition. Most patients with inguinal hernia require surgery. At present, mesh repair is one of the most effective methods to treat inguinal hernia, but insertion of the mesh can cause inflammation. Dexamethasone (DEX) can treat inflammation, but the mechanism by which DEX alleviates inflammation caused by inguinal hernia mesh placement remains unclear. METHOD: We randomly divided rats into groups: negative control (NC), inguinal hernia (IH), polypropylene mesh (PM), DEX treatment, and miR-155 treatment groups. RT-qPCR was performed to determine the expression of miR-155. ELISA was implemented to determine the secretion of IL-1ß, IL-6, and IL-18. Western blotting was used to detect caspase-1, JAK1, p-JAK1, STAT3, and p-STAT3 expression. A dual-luciferase reporter gene array identified a connection between miR-155 and JAK1. RESULTS: The results revealed that the expression of miR-155, IL-1ß, IL-6, and IL-18 was upregulated in the PM group. After DEX treatment, the secretion of miR-155, caspase-1, IL-1ß, IL-6, and IL-18 decreased. Dual luciferase results confirmed that miR-155 induced the targeted downregulation of JAK1, while a miR-155 mimic reversed the therapeutic effect of DEX, and the expression levels of p-JAK1 and p-STAT3 increased. CONCLUSION: DEX regulates the JAK1/STAT3 signaling pathway through miR-155 to relieve inflammation caused by inguinal hernia meshes.

Potential low toxic alternative for Na-Cl cotransporter inhibition: A diuretic effect and mechanism study of Pyrrosia petiolosa.

BACKGROUND: Hydrochlorothiazide, a diuretic commonly used for the treatment of hypertension, is often associated with serious metabolic side effects. Pyrrosia petiolosa (Christ) Ching is a traditional Chinese medicine that possesses diuretic properties, without any obvious side effects. AIM: To evaluate the diuretic effect of P. petiolosa (Christ) Ching and to elucidate its underlying mechanism of action. METHODS: Extracts obtained from different polar components of P. petiolosa (Christ) Ching were analyzed for toxicity in a Kunming mouse model. The diuretic effects of the extracts were compared to that of hydrochlorothiazide in rats. In addition, compound isolation procedures, cell assays of Na-Cl cotransporter inhibition and rat diuretic test of monomeric compounds were conducted to identify the active ingredients in the extract. Subsequently, homology modeling and molecular docking were performed to explain the reason behind the diuretic activity observed. Finally, LC-MS analysis was used to elucidate the underlying mechanism of action of P. petiolosa (Christ) Ching. RESULTS: No toxicity was observed in mice administered P. petiolosa (Christ) Ching extracts. The ethyl acetate fraction showed the most significant diuretic effect. Similar results were obtained during the analysis for Na+ content in rat urine. Further separation of P. petiolosa (Christ) Ching components led to the isolation of methyl chlorogenate, 2',3'-dihydroxy propyl pentadecanoate, and ß-carotene. Results from cell assays showed that the Na-Cl cotransporter inhibitory activity of methyl chlorogenate was greater than that of hydrochlorothiazide. This result was again confirmed by the diuresis tests of monomeric compounds in rats. The molecular simulations explain the stronger interactions between the methyl chlorogenate and Na-Cl cotransporter. Of the compounds determined using LC-MS analysis, 185 were identified to be mostly organic acids. CONCLUSIONS: P. petiolosa possesses significant diuretic activities without any obvious toxicity, with least two possible mechanisms of action. Further study on this herb is warranted.

[Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review].

Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.

[Establishment of a digital remote platform for respiratory support and intelligent early warning in intensive care units].

During the disease progression or treatment of critically ill patients with lung injury, the changes in respiratory mechanics are continuous and dynamic. Establishing a digital platform for respiratory support in the ICU, which enables the continuous recording, dynamic analysis, and real-time alerting of numerical and waveform data from mechanical ventilation, can help intensivists improve their understanding of "dynamic respiratory mechanics", improve respiratory therapy and patient outcomes, as well as reduce workload and increase work efficiency. The construction of a dedicated database for mechanical ventilation, based on ventilator waveforms provides essential data support for projects such as respiratory mechanics data algorithm models. This will facilitate the establishment of an auxiliary decision-making system, enable the realization of intelligent mechanical ventilation, and create a new era of dynamic respiratory mechanics.

[Applications and challenges of large language models in critical care medicine].

The rapid development of big data methods and technologies has provided more and more new ideas and methods for clinical diagnosis and treatment. The emergence of large language models (LLM) has made it possible for human-computer interactive dialogues and applications in complex medical scenarios. Critical care medicine is a process of continuous dynamic targeted treatment. The huge data generated in this process needs to be integrated and optimized through models for clinical application, interaction in teaching simulation, and assistance in scientific research. Using the LLM represented by generative pre-trained transformer ChatGPT can initially realize the application in the diagnosis of severe diseases, the prediction of death risk and the management of medical records. At the same time, the time and space limitations, illusions and ethical and moral issues of ChatGPT emerged as the times require. In the future, it is undeniable that it may play a huge role in the diagnosis and treatment of critical care medicine, but the current application should be combined with more clinical knowledge reserves of critical care medicine to carefully judge its conclusions.

Octahedral Distortion and Displacement-Type Ferroelectricity with Switchable Photovoltaic Effect in a 3d

Because of the half-filled t_{2g}-electron configuration, the BO_{6} octahedral distortion in a 3d^{3} perovskite system is usually very limited. In this Letter, a perovskitelike oxide Hg_{0.75}Pb_{0.25}MnO_{3} (HPMO) with a 3d^{3} Mn^{4+} state was synthesized by using high pressure and high temperature methods. This compound exhibits an unusually large octahedral distortion enhanced by approximately 2 orders of magnitude compared with that observed in other 3d^{3} perovskite systems like RCr^{3+}O_{3} (R=rare earth). Essentially different from centrosymmetric HgMnO_{3} and PbMnO_{3}, the A-site doped HPMO presents a polar crystal structure with the space group Ama2 and a substantial spontaneous electric polarization (26.5 µC/cm^{2} in theory) arising from the off-center displacements of A- and B-site ions. More interestingly, a prominent net photocurrent and switchable photovoltaic effect with a sustainable photoresponse were observed in the current polycrystalline HPMO. This Letter provides an exceptional d^{3} material system which shows unusually large octahedral distortion and displacement-type ferroelectricity violating the "d^{0}-ness" rule.

A systematic review and meta-analysis of risk factors associated with healthcare-associated infections among hospitalized patients in Chinese general hospitals from 2001 to2022.

BACKGROUND: Healthcare-associated infections (HAIs) are a serious global public health issue. However, a comprehensive analysis of risk factors for HAIs has yet been undertaken at a large scale among general hospitals in China. The aim of this review was to assess risk factors associated with HAIs in Chinese general hospitals. METHODS: Medline, EMBASE and Chinese Journals Online databases were searched to find studies published from 1st January 2001 to 31st May 2022. The random-effects model was used to estimate odds ratio (OR). Heterogeneity was assessed based on the τˆ2 and I2 statistics. RESULTS: A total of 5037 published papers were identified from the initial search and 58 studies were included in the quantitative meta-analysis; 1,211,117 hospitalized patients were incorporated covering 41 regions in 23 provinces of China and 29,737 were identified as having HAIs. Our review showed that HAIs were significantly associated with sociodemographic characteristics including age older than 60 years (OR: 1.74 (1.38-2.19)) and male sex (1.33 (1.20-1.47)); invasive procedures (3.54 (1.50-8.34)); health conditions such as chronic diseases (1.49 (1.22-1.82)), coma (OR: 5.12 (1.70-15.38)) and immunosuppression (2.45 (1.55-3.87)). Other risk factors included long-term bed (5.84 (5.12-6.66)), and healthcare-related risk factors such as chemotherapy (1.96 (1.28-3.01)), haemodialysis (3.12 (1.80-5.39)), hormone therapy (2.96(1.96-4.45)), immunosuppression (2.45 (1.55-3.87)) and use of antibiotics (6.64 (3.16-13.96)), and longer than 15 hospitalization days (13.36 (6.80-26.26)). CONCLUSIONS: Being male and aged over 60 years, invasive procedure, health conditions, healthcare-related risk factors, and longer than 15 hospitalization days were the main risk factors associated with HAIs in Chinese general hospitals. This supports the evidence base to inform the relevant cost-effective prevention and control strategies.

[Effect of hemoperfusion on protein energy wasting and long-term prognosis in patients on maintenance hemodialysis].

Objective: To explore the effect of hemoperfusion (HP) combined with hemodialysis (HD) (HD+HP) on protein energy wasting (PEW) and long-term prognosis in patients on maintenance HD (MHD). Methods: A prospective multicenter cohort study was conducted. Adult MHD patients who completed PEW assessment and underwent regular dialysis between July 2015 and July 2021 at 23 hemodialysis centers in Guizhou Province were selected. Demographic characteristics, physical indicators, laboratory indicators, 3-day diet diary and HP treatment data of the subjects were collected. The patients were divided into different groups according to the presence or absence of HP, the frequency of HP treatment and the type of cartridge, and then relevant indicators were compared. Multivariate logistic regression model and Cox proportional regression model were used to analyze the influence of HP treatment on PEW risk in MHD patients. Meanwhile, Kaplan-Meier method was used to plot the survival curve. Results: A total of 4 623 MHD patients (2 789 males and 1 834 females) aged (53.7±15.9) years were included in the study, with a median dialysis age of 64.3 (44.3, 92.3) months. There were 3 429 (74.2%) MHD patients treated with HD+HP, and 1 194 patients (25.8%) were not treated with HP. According to the 2008 diagnostic criteria of the International Society for Renal Nutrition and Metabolism (ISRNM), the incidence of PEW was 26.0% (1 204/4 623). Multivariate logistic regression analysis showed that female (OR=2.48, 95%CI: 1.55-3.95, P<0.001), diabetes (OR=1.75, 95%CI: 1.08-2.83, P=0.024) and high-sensitivity C-reactive protein (hs-CRP) (OR=1.02, 95%CI: 1.01-1.03, P=0.003) were risk factors for PEW, while treatment with HD+HP (OR=0.51, 95%CI: 0.31-0.87, P=0.012) and elevated triglyceride levels (OR=0.62, 95%CI: 0.48-0.80, P<0.001) were protective factors. Cox hazard ratio regression showed that among different HP treatment frequencies and cartridge types, 2 times/month (HR=0.40, 95%CI: 0.17-0.95, P=0.037), 3 times/month (HR=0.44, 95%CI: 0.23-0.85, P=0.014), 4 times/month (HR=0.54, 95%CI: 0.34-0.85, P=0.008), HA130 (HR=0.57, 95%CI: 0.36-0.89, P=0.014) and HA230 (HR=0.30, 95%CI: 0.15-0.63, P=0.001) had protective effects on the occurrence of PEW in MHD patients. The all-cause mortality rate was 11.3% (521/4 623) at 33 (24, 48) months of follow-up. Kaplan-Meier analysis showed that patients undergoing 4 times/month HP treatment (χ2=36.78, P<0.001) and using HA230 (χ2=9.46, P=0.002) had the highest survival rate. Conclusion: Treatment with HD+HP is a protective factor for PEW in patients with MHD, and 4 times/month HP treatment or HA230 significantly reduces the risk of PEW and all-cause mortality in patients with MHD.

[Effects of novel bioactive glasses on promoting remineralization of artificial dentin caries].

OBJECTIVE: To investigate the effects of novel bioactive glasses (BG) including PSC with high phosphorus component and FBG with fluorine-doped element on promoting remineralization of artificial dentin caries. METHODS: (1) BGs were used in this study as follows: PSC (10.8%P2O5-54.2%SiO2-35.0%CaO, mol.%) were synthesized using phytic acid as the phosphorus precursor through sol-gel method. FBG (6.1%P2O5-37.0%SiO2-53.9%CaO-3.0%CaF2, mol.%) and 45S5(6.0%P2O5-45.0%SiO2-24.5%CaO-24.5%Na2O, mol.%) were synthesized by traditional melt method. (2) The above BGs were soaked in simulated body fluid (SBF) for 24 hours. Then X-ray diffraction (XRD) was used to analyze the formation of hydroxyapatite (HA) crystals. (3) Prepared 1 mm thick dentin slices were soaked in 17% ethylene diamine tetraacetic acid (EDTA) for 1 week to demineralize the dentin. Then the dentin slices treated by BG were soaked in SBF for 1 week. Field emission scanning electron micro-scopy (FE-SEM) was used to observe the surface morphology of the dentin slices. (4) Four cavities were prepared to 1 mm depth in each 2 mm thick dentin slice, then were treated with lactic acid for 2 weeks to form the artificial dentin caries. Wax, mineral trioxide aggregate (MTA), PSC and FBG were used to fill four cavities as blank control group, MTA group, PSC group and FBG group respectively. Then the spe-cimens were soaked in SBF for 4 weeks. The changes of depth and density of demineralized dentin were analyzed using Micro-CT before filling and after 2 and 4 weeks filling. RESULTS: (1) PSC and FBG promoted mineral formation on the surfaces of the demineralized dentin. And the speed was faster and crystallinity was higher in PSC group than the FBG and 45S5 groups. (2) The increased mineral density of artificial dentin caries in PSC group were (185.98 ± 55.66) mg/cm3 and (213.64 ± 36.01) mg/cm3 2 and 4 weeks after filling respectively, which were significantly higher than the control group [(20.38 ± 7.55) mg/cm3, P=0.006; (36.46 ± 10.79) mg/cm3, P=0.001]. At meanwhile, PSC group was also higher than MTA group [(57.29 ± 10.09) mg/cm3; (111.02 ± 22.06) mg/cm3], and it had statistical difference (P=0.015; P=0.006). The depth of remineralized dentin in PSC group were (40.0 ± 16.9) µm and (54.5 ± 17.8) µm 2 and 4 weeks respectively, which were also statistically different from the control group (P =0.010;P=0.001). There were no statistical differences between the control group and MTA group. The above effects of FBG group were between PSC and MTA. CONCLUSION: PSC has advantages in the speed, quality and depth of mineral deposition in the demineralized layer of artificial dentin caries. It would be expected to be an ideal material to promote the remineralization of dentin caries.

[A case of ocular albinism with an abnormal visual evoked potential].

A 16-year-old male patient had poor binocular vision, alternating exotropia, horizontal nystagmus, and no obvious pigmentation loss in the eyes and other parts of the body. Optical coherence tomographic examination showed no normal central macular depression. The three-channel flash visual evoked potential method was used to examine each eye. The left and right channel reactions were found to be significantly asymmetric, and the clinical diagnosis was ocular albinism.