Comparison of balanced crystalloids versus normal saline in patients with diabetic ketoacidosis: a meta-analysis of randomized controlled trials.

Purpose: The optimal resuscitative fluid for patients with diabetic ketoacidosis (DKA) remains controversial. Therefore, our objective was to assess the effect of balanced crystalloids in contrast to normal saline on clinical outcomes among patients with DKA. Methods: We searched electronic databases for randomized controlled trials comparing balanced crystalloids versus normal saline in patients with DKA, the search period was from inception through October 20th, 2023. The outcomes were the time to resolution of DKA, major adverse kidney events, post-resuscitation chloride, and incidence of hypokalemia. Results: Our meta-analysis encompassed 11 trials, incorporating a total of 753 patients with DKA. There was no significant difference between balanced crystalloids and normal saline group for the time to resolution of DKA (MD -1.49, 95%CI -4.29 to 1.31, P=0.30, I2 = 65%), major adverse kidney events (RR 0.88, 95%CI 0.58 to 1.34, P=0.56, I2 = 0%), and incidence of hypokalemia (RR 0.80, 95%CI 0.43 to 1.46, P=0.46, I2 = 56%). However, there was a significant reduction in the post-resuscitation chloride (MD -3.16, 95%CI -5.82 to -0.49, P=0.02, I2 = 73%) among patients received balanced crystalloids. Conclusion: Among patients with DKA, the use of balanced crystalloids as compared to normal saline has no effect on the time to resolution of DKA, major adverse kidney events, and incidence of hypokalemia. However, the use of balanced crystalloids could reduce the post-resuscitation chloride. Systematic review registration: https://osf.io, identifier c8f3d.

A chromosome-level haplotype-resolved genome assembly of oriental tobacco budworm (Helicoverpa assulta).

Oriental tobacco budworm (Helicoverpa assulta) and cotton bollworm (Helicoverpa armigera) are two closely related species within the genus Helicoverpa. They have similar appearances and consistent damage patterns, often leading to confusion. However, the cotton bollworm is a typical polyphagous insect, while the oriental tobacco budworm belongs to the oligophagous insects. In this study, we used Nanopore, PacBio, and Illumina platforms to sequence the genome of H. assulta and used Hifiasm to create a haplotype-resolved draft genome. The Hi-C technique helped anchor 33 primary contigs to 32 chromosomes, including two sex chromosomes, Z and W. The final primary haploid genome assembly was approximately 415.19 Mb in length. BUSCO analysis revealed a high degree of completeness, with 99.0% gene coverage in this genome assembly. The repeat sequences constituted 38.39% of the genome assembly, and we annotated 17093 protein-coding genes. The high-quality genome assembly of the oriental tobacco budworm serves as a valuable genetic resource that enhances our comprehension of how they select hosts in a complex odour environment. It will also aid in developing an effective control policy.

Enhanced biodegradation of phenol under Cr(VI) stress by microbial collaboration and potential application of machine learning for phenol biodegradation.

Cr(VI) and phenol commonly coexist in wastewater, posing a great threat to the environment and human health. However, it is still a challenge for microorganisms to degrade phenol under high Cr(VI) stress. In this study, the phenol-degrading strain Bacillus cereus ZWB3 was co-cultured with the Cr(VI)-reducing strain Bacillus licheniformis MZ-1 to enhance phenol biodegradation under Cr(Ⅵ) stress. Compared with phenol-degrading strain ZWB3, which has weak tolerance to Cr(Ⅵ), and Cr(Ⅵ)-reducing strain MZ-1, which has no phenol-degrading ability, the co-culture of two strains could significantly increase the degraded rate and capacity of phenol. In addition, the co-cultured strains exhibited phenol degradation ability over a wide pH range (7-10). The reduced content of intracellular proteins and polysaccharides produced by the co-cultured strains contributed to the enhancement of phenol degradation and Cr(Ⅵ) tolerance. The determination coefficients R2, RMSE, and MAPE showed that the BP-ANN model could predict the degradation of phenol under various conditions, which saved time and economic cost. The metabolic pathway of microbial degradation of phenol was deduced by metabolic analysis. This study provides a valuable strategy for wastewater treatment containing Cr(Ⅵ) and phenol.

Measurements of 131I activity in thyroid of workers at the place of radioiodine therapy in 38 hospitals in China.

To investigate the levels of 131I activity in thyroid of workers at the place of radioiodine therapy and their main influential factors in China, 341 workers at 38 hospitals performing radioiodine therapy procedure in five provinces were recruited to be measured in 2021. A hand-held gamma spectrometer with NaI(Tl) probe was plastered to the thyroids and thighs of the subjects during the measurement, and each measurement time was 120 s. The internal exposure dose was calculated, and the committed effective dose was estimated. In 86 (25.22%) of the 341 examined workers, 131I thyroid activity was above minimum detectable activity (MDA, 26.6 Bq). The maximum activity was 4.9 × 103 Bq. The detection results above MDA were at 22 (57.89%) different hospitals. The detectable rate for private hospitals (4.8%) was significantly lower than that for public hospitals (26.6%), P < 0.05. The detectable rate for hospitals in provincial capital cities (15.4%) was significantly lower than in nonprovincial capital cities (41.7%), P < 0.001. The detectable rate for hospitals engaged in 131I therapy for thyroid cancer (31.2%) was significantly higher than only for hyperthyroidism (10.3%), P < 0.001. A total of 32 subjects' committed effective dose might exceed 1 mSv. Results indicated the 131I activity in the thyroid of workers at the place of radioiodine varied considerably in China, and mainly related to ownership, location and therapy program of the hospitals.

Display of porcine epidemic diarrhea virus spike protein B-cell linear epitope on Lactobacillus mucosae G01 S-layer surface induce a robust immunogenicity in mice.

The Porcine epidemic diarrhea virus (PEDV) presents a substantial risk to the domestic pig industry, resulting in extensive and fatal viral diarrhea among piglets. Recognizing the mucosal stimulation triggered by PEDV and harnessing the regulatory impact of lactobacilli on intestinal function, we have developed a lactobacillus-based vaccine that is carefully designed to elicit a strong mucosal immune response. Through bioinformatics analysis, we examined PEDV S proteins to identify B-cell linear epitopes that meet the criteria of being non-toxic, soluble, antigenic, and capable of neutralizing the virus. In this study, a genetically modified strain of Lactobacillus mucosae G01 (L.mucosae G01) was created by utilizing the S layer protein (SLP) as a scaffold for surface presentation. Chimeric immunodominant epitopes with neutralizing activity were incorporated at various sites on SLP. The successful expression of SLP chimeric immunodominant epitope 1 on the surface of L.mucosae G01 was confirmed through indirect immunofluorescence and transmission electron microscopy, revealing the formation of a transparent membrane. The findings demonstrate that the oral administration of L.mucosae G01, which expresses the SLP chimeric immunodominant gene epitope1, induces the production of secreted IgA in the intestine and feces of mice. Additionally, there is an elevation in IgG levels in the serum. Moreover, the levels of cytokines IL-2, IL-4, IFN-γ, and IL-17 are significantly increased compared to the negative control group. These results suggest that L. mucosae G01 has the ability to deliver exogenous antigens and elicit a specific mucosal immune response against PEDV. This investigation presents new possibilities for immunoprophylaxis against PEDV-induced diarrhea.

Prevalence, Time of Infection, and Diversity of Porcine Reproductive and Respiratory Syndrome Virus in China.

Porcine reproductive and respiratory syndrome virus (PRRVS) is a major swine viral pathogen that affects the pig industry worldwide. Control of early PRRSV infection is essential, and different types of PRRSV-positive samples can reflect the time point of PRRSV infection. This study aims to investigate the epidemiological characteristics of PRRSV in China from Q4 2021 to Q4 2022, which will be beneficial for porcine reproductive and respiratory syndrome virus (PRRSV)control in the swine production industry in the future. A total of 7518 samples (of processing fluid, weaning serum, and oral fluid) were collected from 100 intensive pig farms in 21 provinces, which covered all five pig production regions in China, on a quarterly basis starting from the fourth quarter of 2021 and ending on the fourth quarter of 2022. Independent of sample type, 32.1% (2416/7518) of the total samples were PCR-positive for PRRSV, including 73.6% (1780/2416) samples that were positive for wild PRRSV, and the remaining were positive for PRRSV vaccine strains. On the basis of the time of infection, 58.9% suckling piglets (processing fluid) and 30.8% weaning piglets (weaning serum) showed PRRSV infection at an early stage (approximately 90% of the farms). The sequencing analysis results indicate a wide range of diverse PRRSV wild strains in China, with lineage 1 as the dominant strain. Our study clearly demonstrates the prevalence, infection stage, and diversity of PRRSV in China. This study provides useful data for the epidemiological understanding of PRRSV, which can contribute to the strategic and systematic prevention and control of PRRSV in China.

Allergic bronchopulmonary mycosis due to Schizophyllum commune in a patient with chronic hepatitis B.

INTRODUCTION: Schizophyllum commune (S. commune) is an opportunistic pathogenic fungus and can cause infection of the respiratory system in immunocompromised hosts. Allergic bronchopulmonary mycosis (ABPM) is the major disease caused by S. commune. However, identification of S. commune using routine mycological diagnostic methods is difficult. It is easy to make mistakes in diagnosis and treatment, resulting in deterioration of the disease. We report the first case of ABPM due to S. commune in a Chinese patient with chronic hepatitis B. CASE PRESENTATION: The patient presented cough, sputum and dyspnea for six months. The pathogen was missed during routine laboratory workup. We performed bronchoscopy examination and bronchoalveolar lavage. S. commune was identified by metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid (BALF). Hence, the patient was immediately treated with 200 mg voriconazole twice daily (intravenous infusion) and 20 mg prednisone once a day (oral therapy), along with oral entecavir for hepatitis B. There was no recurrence of infection after the medication was discontinued. CONCLUSIONS: S. commune infection should be considered in the diagnosis of patients with refractory cough, sputum and dyspnea, especially in immunocompromised individuals. The mNGS technique is an effective supplementary technique for the diagnosis of S. commune infection, enabling precise clinical decision-making and appropriate treatment. Most patients have good prognosis with a combination of proper antifungal therapy and hormonal therapy.

Improved antioxidative and antibacterial activity of epigallocatechin gallate derivative complexed by zinc cations and chitosan.

Epigallocatechin gallate (EGCG) has attracted increasing attention thanks to its multi-bioactivities, and people are keen on improving the antioxidative and antibacterial performance of EGCG. Based on the favorable biofunctionality of Zn2+ and chitosan (CS), an EGCG derivative with a novel formula, i.e., EGCG-Zn-CS, is presented in this study. The structure of EGCG-Zn-CS was characterized by FT-IR, UV-vis, TGA, XPS, and SEM-EDS. The radical elimination results indicate that 0.1 mg mL-1 of EGCG-Zn-CS demonstrates DPPH radical and hydroxyl radical scavenging activities of 94.8% and 92.3%, while 0.1 mg mL-1 of EGCG exhibits only 78.5% and 75.6%, respectively, which means improved antioxidative activity of EGCG-Zn-CS was obtained. Inhibitory experiments against Staphylococcus aureus and Escherichia coli reveal that the minimal inhibitory concentrations (MICs) of EGCG-Zn-CS were 15.625 µg mL-1 and 187.5 µg mL-1, whereas the minimal bactericide concentrations (MBCs) were 46.875 µg mL-1 and 750 µg mL-1, respectively, which indicate that EGCG-Zn-CS exerts much higher antibacterial activity than EGCG. It can be concluded that the complexing of zinc cations and CS could amazingly improve both the antioxidative and antibacterial activity of EGCG, and it is expected that an exploration of EGCG-Zn-CS may inspire the development of simultaneous effective antioxidant and antibacterial agents.

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Analysis and Functional Prediction of Core Bacteria in the Arabidopsis Rhizosphere Microbiome under Drought Stress.

The effects of global warming, population growth, and economic development are increasing the frequency of extreme weather events, such as drought. Among abiotic stresses, drought has the greatest impact on soil biological activity and crop yields. The rhizosphere microbiota, which represents a second gene pool for plants, may help alleviate the effects of drought on crops. In order to investigate the structure and diversity of the bacterial communities on drought stress, this study analyzed the differences in the bacterial communities by high-throughput sequencing and bioinformatical analyses in the rhizosphere of Arabidopsis thaliana under normal and drought conditions. Based on analysis of α and ß diversity, the results showed that drought stress had no significant effect on species diversity between groups, but affected species composition. Difference analysis of the treatments showed that the bacteria with positive responses to drought stress were Burkholderia-Caballeronia-Paraburkholderia (BCP) and Streptomyces. Drought stress reduced the complexity of the rhizosphere bacterial co-occurrence network. Streptomyces was at the core of the network in both the control and drought treatments, whereas the enrichment of BCP under drought conditions was likely due to a decrease in competitors. Functional prediction showed that the core bacteria metabolized a wide range of carbohydrates, such as pentose, glycans, and aromatic compounds. Our results provide a scientific and theoretical basis for the use of rhizosphere microbial communities to alleviate plant drought stress and the further exploration of rhizosphere microbial interactions under drought stress.

Fine-Tuning Crystal Structures of Lead Bromide Perovskite Nanocrystals through Trace Cadmium(II) Doping for Efficient Color-Saturated Green LEDs.

Decreasing perovskite nanocrystal size increases radiative recombination due to the quantum confinement effect, but also increases the Auger recombination rate which leads to carrier imbalance in the emitting layers of electroluminescent devices. Here, we overcome this trade-off by increasing the exciton effective mass without affecting the size, which is realized through the trace Cd2+ doping of formamidinium lead bromide perovskite nanocrystals. We observe an ~2.7 times increase in the exciton binding energy benefiting from a slight distortion of the [BX6]4- octahedra caused by doping in the case of that the Auger recombination rate is almost unchanged. As a result, bright color-saturated green emitting perovskite nanocrystals with a photoluminescence quantum yield of 96 % are obtained. Cd2+ doping also shifts up the energy levels of the nanocrystals, relative to the Fermi level so that heavily n-doped emitters convert into only slightly n-doped ones; this boosts the charge injection efficiency of the corresponding light-emitting diodes. The light-emitting devices based on those nanocrystals reached a high external quantum efficiency of 29.4 % corresponding to a current efficiency of 123 cd A-1, and showed dramatically improved device lifetime, with a narrow bandwidth of 22 nm and Commission Internationale de I'Eclairage coordinates of (0.20, 0.76) for color-saturated green emission for the electroluminescence peak centered at 534 nm, thus being fully compliant with the latest standard for wide color gamut displays.

The role of MrUbp4, a deubiquitinase, in conidial yield, thermotolerance, and virulence in Metarhizium robertsii.

Ubiquitin-specific proteases (UBPs), the largest subfamily of deubiquitinating enzymes, regulate ubiquitin homeostasis and play diverse roles in eukaryotes. Ubp4 is essential for the growth, development, and pathogenicity of various fungal pathogens. However, its functions in the growth, stress responses, and virulence of entomopathogenic fungi remain unclear. In this study, we elucidated the role of the homolog of Ubp4, MrUbp4, in the entomopathogenic fungus Metarhizium robertsii. Deletion of MrUbp4 led to a notable increase in ubiquitination levels, demonstrating the involvement of MrUbp4 in protein deubiquitination. Furthermore, the ΔMrUbp4 mutant displayed a significant reduction in conidial yield, underscoring the pivotal role of MrUbp4 in conidiation. Additionally, the mutant exhibited heightened resistance to conidial heat treatment, emphasizing the role of MrUbp4 in thermotolerance. Notably, insect bioassays unveiled a substantial impairment in the virulence of the ΔMrUbp4 mutant. This was accompanied by a notable decrease in cuticle penetration ability and appressorium formation upon further analysis. In summary, our findings highlight the essential role of MrUbp4 in regulating the conidial yield, thermotolerance, and contributions to the virulence of M. robertsii.

Yingxiang Acupoint Embedding Improves Mucosal Barrier Function in Rats with Local Allergic Rhinitis.

INTRODUCTION: Epithelial barrier disruption is the initial cause of various diseases. We previously reported that acupoint catgut embedding (AE) improves tight junction proteins (TJs) in rats with allergic rhinitis. However, whether AE improves the epithelial barrier in local allergic rhinitis (LAR) remains unknown. METHODS: A total of 36 Sprague Dawley (SD) male rats aged 5-7 weeks were divided into 6 groups with 6 rats each: control group, LAR model group, false acupoint embedding + LAR group, acupoint embedding + LAR group, capsaicin + LAR group, and tunicamycin + acupoint embedding + LAR group. Behavioral observation, ELISA to detect inflammatory factors in nasal lavage fluid and serum IgE, nasal mucosal permeability test, hematoxylin-eosin staining, PCR to detect Substance P (SP), Western blot, and immunofluorescence to detect endoplasmic reticulum stress (ERS) index and TJs were used to investigate the mechanism of AE in LAR. RESULTS: AE improved the symptoms and pathological features of nasal mucosa of LAR rats, reduced the inflammatory factors (IL4, IL5, IL13) of nasal lavage fluid, and showed no significant change in serum IgE levels in all groups. In addition, AE decreased the expression of SP in nasal mucosa of LAR rats, inhibited ERS, increased the expression of tight junction protein, reduced the permeability of nasal mucosa, and improved the function of nasal mucosal barrier. CONCLUSION: This study confirms that AE can improve the nasal mucosal barrier function of LAR by reducing the expression of SP, inhibiting ERS and increasing the expression of TJs, thus enhancing the nasal mucosal barrier function.

Efficacy of fire needle combined with 308 nm excimer laser therapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Vitiligo is a common depigmenting skin disorder. This work is performed to systematically evaluate the efficacy and safety of fire needles combined with 308 nm excimer laser therapy in treating vitiligo. METHODS: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on fire needles combined with 308 nm excimer laser therapy with 308 nm excimer laser therapy alone for vitiligo were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes. RESULTS: In this study, 10 RCTs and 1333 patients were included. The results showed that compared with 308 nm excimer laser therapy alone, fire needle combined with 308 nm excimer laser therapy is more effective in improving clinical effective rate (RR = 1.36, 95% CI [1.24, 1.50], p < 0.00001), serum CD4+ level (MD = 3.12, 95% CI [2.50, 3.74], p < 0.00001), CD4+/CD8+ ratio (MD = 0.24, 95% CI [0.09, 0.39], p = 0.001), and quality of life measured by the Dermatology Life Quality Index (DLQI) (MD = 3.76, 95% CI [3.33, 4.19], p < 0.00001), and reducing the Vitiligo Area Score Index (VASI) (MD = -5.47, 95% CI [-6.56, -4.37], p < 0.00001). The reported adverse events, including redness, swelling, pain, blisters, and itching, were controllable, and all these events were well tolerated. CONCLUSION: The current evidence indicates that fire needle combined with 308 nm excimer laser therapy is effective and safe for vitiligo. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy.

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. The host immune system recognizes viral pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly in the cytoplasm, cyclic GMP-AMP synthase (cGAS) senses and binds virus DNA and subsequently activates stimulator of interferon genes (STING) to trigger a series of intracellular signalling cascades to defend against invading pathogenic microorganisms. Integrated omic and functional analyses identify the cGAS-STING pathway regulating various host cellular responses and controlling viral infections. Aside from its most common function in regulating inflammation and type I interferon, a growing body of evidence suggests that the cGAS-STING signalling axis is closely associated with a series of cellular responses, such as oxidative stress, autophagy, and endoplasmic reticulum stress, which have major impacts on physiological homeostasis. Interestingly, these host cellular responses play dual roles in the regulation of the cGAS-STING signalling axis and the clearance of viruses. Here, we outline recent insights into cGAS-STING in regulating type I interferon, inflammation, oxidative stress, autophagy and endoplasmic reticulum stress and discuss their interactions with viral infections. A detailed understanding of the cGAS-STING-mediated potential antiviral effects contributes to revealing the pathogenesis of certain viruses and sheds light on effective solutions for antiviral therapy.

Wearable sampling of proteins from human exhaled aerosols for nano-liquid chromatography-tandem mass spectrometry analysis: A pilot study.

RATIONALE: Human exhaled breath usually contains unique proteins that may provide clues to characterize individual physiological activities and many diseases. However, the concentration of exhaled proteins in exhaled breath is extremely low and usually does not reach the detection limits of all online breath mass spectrometry instruments. Therefore, developing a new breath sampler for collecting and characterizing exhaled proteins is important. METHODS: In this study, a new mask-based wearable sampler was developed by fixing metal materials into the inner surface of the KN95 mask. Human exhaled proteins could be directly adsorbed onto the metal material while wearing the mask. After sampling, the collected proteins were eluted, digested, and identified using nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS). RESULTS: The adsorption of exhaled proteins was evaluated, showing that modified gold foil is an effective material for collecting exhaled proteins. Various endogenous proteins were successfully identified from exhaled breath, many of which can be potential biomarkers for disease diagnosis. CONCLUSIONS: By coupling the newly developed mask sampler with nano-LC-MS/MS, human exhaled proteins were successfully collected and identified. Our results show that the mask sampler is wearable, simple, and convenient, and the method is noninvasive for investigating disease diagnosis and human health.

Beclin-1-Derived Peptide MP1 Attenuates Renal Fibrosis by Inhibiting the Wnt/ß-Catenin Pathway.

Renal fibrosis is distinguished by the abnormal deposition of extracellular matrix and progressive loss of nephron function, with a lack of effective treatment options in clinical practice. In this study, we discovered that the Beclin-1-derived peptide MP1 significantly inhibits the abnormal expression of fibrosis and epithelial-mesenchymal transition-related markers, including α-smooth muscle actin, fibronectin, collagen I, matrix metallopeptidase 2, Snail1, and vimentin both in vitro and in vivo. H&E staining was employed to evaluate renal function, while serum creatinine (Scr) and blood urea nitrogen (BUN) were used as main indices to assess pathologic changes in the obstructed kidney. The results demonstrated that daily treatment with MP1 during the 14-day experiment significantly alleviated renal dysfunction and changes in Scr and BUN in mice with unilateral ureteral obstruction. Mechanistic research revealed that MP1 was found to have a significant inhibitory effect on the expression of crucial components involved in both the Wnt/ß-catenin and transforming growth factor (TGF)-ß/Smad pathways, including ß-catenin, C-Myc, cyclin D1, TGF-ß1, and p-Smad/Smad. However, MP1 exhibited no significant impact on either the LC3II/LC3I ratio or P62 levels. These findings indicate that MP1 improves renal physiologic function and mitigates the fibrosis progression by inhibiting the Wnt/ß-catenin pathway. Our study suggests that MP1 represents a promising and novel candidate drug precursor for the treatment of renal fibrosis. SIGNIFICANCE STATEMENT: This study indicated that the Beclin-1-derived peptide MP1 effectively mitigated renal fibrosis induced by unilateral ureteral obstruction through inhibiting the Wnt/ß-catenin pathway and transforming growth factor-ß/Smad pathway, thereby improving renal physiological function. Importantly, unlike other Beclin-1-derived peptides, MP1 exhibited no significant impact on autophagy in normal cells. MP1 represents a promising and novel candidate drug precursor for the treatment of renal fibrosis focusing on Beclin-1 derivatives and Wnt/ß-catenin pathway.

Pharmacological effects and target analysis of Guipi wan in the treatment of cerebral ischemia-reperfusion injury.

Guipi wan (GPW) is a traditional Chinese medicine commonly used in clinical practice, typically to treat neurological diseases such as neurasthenia and traumatic brain injury. It may have positive effects on cerebral ischemia‒reperfusion injury (cI/R). This study aimed to assess the effects of GPW in a mouse model of cI/R and find its possible targets. C57BL/6J mice were used to establish the cI/R model, and the laser speckle doppler was used to determine the success of the model. GPW was administered intragastrically for 7 days, brain tissue sections were stained with TTC, HE, and TUNEL, Western blot assay was performed to detect the effect of apoptosis-related proteins. Furthermore, we screened active ingredients from the TCM Database and constructed a compound‒target network using the Cytoscape 3.8.0 software. Moreover, we employed protein‒protein interaction and component‒target‒pathway network analyses to determine the potential components of GPW and its target genes, the key target was verified through molecular docking. Finally, we detected the influence of the downstream signaling pathway of the target through Western blot. The results showed that GPW decreased the cerebral infarction area, neurological function scores, and neuronal apoptosis in mice by regulating PI3K/AKT signaling pathway. Network analysis indicated that gamma-aminobutyric acid B receptor 1 (GABBR1) might be a potential target for the treatment of cI/R. Molecular docking indicated that 9 active components in GPW could bind to GABBR1 with desirable binding energy. This study represented the demonstratable effect of GPW in the treatment of cI/R injury and suggested GABBR1 as a potential target using network analysis.

Symptom clusters and nutritional status in primary liver cancer patients receiving TACE.

INTRODUCTION: symptom clusters (SCs) are highly prevalent among patients diagnosed with primary liver cancer. Malnutrition poses a heightened risk for a more pronounced total symptom cluster score. OBJECTIVE: this study aimed to identify SCs and assess the nutritional status of patients undergoing transcatheter arterial chemoembolization (TACE). Furthermore, it aimed to investigate the association between nutritional status and symptom clusters. METHODS: primary liver cancer patients who were scheduled to receive TACE were recruited. Symptoms data were collected using the MD Anderson Symptom Inventory (MDASI-C) and the Symptom Module specific to Primary Cancer (TSM-PLC). Nutritional assessment relied on the Nutritional Risk Screening-2002 (NRS-2002) and blood biochemistry. The SCs were extracted using exploratory factor analysis, while the relationship between SCs and nutritional status was evaluated using Spearman correlation analysis. RESULTS: the study included 226 patients, four distinct symptom clusters emerged: emotional-psychological symptom cluster, upper gastrointestinal symptom cluster, post-embolization-related symptom cluster, and liver function impairment symptom cluster. 68.14 % of patients were found to be at high risk of malnutrition. Our study revealed significant differences in Scs scores between patients at risk of malnutrition and those without such risk (p < 0.050). Notably, we observed a positive correlation between NRS-2002 scores and the scores of all symptom clusters (r = 0.205 to 0.419, p < 0.001), while a negative correlation was observed between prealbumin levels and the scores of all symptom clusters (r = -0.183 to -0.454, p < 0.001). CONCLUSION: the study highlights the high risk of malnutrition among liver cancer patients receiving TACE and the positive correlation between high malnutrition risk and Scs scores.