Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective To study the effects of the intelligent hearing-assistive system incorporated in Nuro-tron cochlear implants(CI),including the autonomic acoustic scene recognition(ASR),intelligent strategy config-uration as well as the objective and subjective hearing improvements on recipients.Methods ① To evaluate the per-formance of the ASR matule,in a sound-proof room,the preset five kinds of test audios,including speech,noise,speech in noise,pure music(without human voice)and non-pure Music(with human voice)were played.Each type of scenes included 6 to 9 5 min test files.The prediction accuracy and scene switching times were calculated.② In order to evaluate the noise-reduction performance of the ABeam technology in the speech enhancement module,13 Nurotron? CI recipients were recruited and their speech recognition rate when ABeam was"ON"and"OFF"with noise coming from 90°,180°or 270°were tested,individually.Also,their subjective hearing feedback was evaluated through visual analogue scale(VAS)evaluation.Results The ASR module achieved high prediction performance,with prediction accuracy 99％±4％,96％±9％,94％±12％,94％±15％,92％±13％for speech,noise,noisy speech,pure music and non-pure music,respectively.The scene transation times for each individual scene were 1.1 ±0.3,1.4±0.7,1.3±0.5,1.4±0.8 and 1.3±0.5,indicating that the prediction was also stable.When noise came from the sides and behind of recipients and speech signal from the front,the adaptive dual microphone noise re-duction algorithm ABeam significantly increased the speech recognition score(SRS)in 5 dB signal-to-noise(SNR)environment(P＜0.001),with an average increase of 15.92％.Especially when the noise came from 180 degree backward,the SRS increased 28.68％when ABeam was"0N",which was significantly higher than when ABeam was"OFF"(P＜0.01).Conclusion The intelligent hearing-assistive system can help CI recipients automatically configure appropriate SPSs under different environments,improving the speech intelligibility and hearing comfort.

Malacoplakia is a rare granuloma disease mainly occurred in the urinary system, it is even rarer for renal malacoplakia invading the descending colon complicated with bladder malacoplakia. In this study, one such case was reported. Imaging examination suggested that the left kidney was a large patchy mixed density shadow, and enhancement scan lesion was uneven enhancement. CT guided renal puncture biopsy was performed, and postoperative pathology suggested renal malacoplakia. Transurethral cystoscopy was performed, and postoperative pathology confirmed that it was malacoplakia of the bladder. The effect of conservative antibiotic treatment was not good. The patient underwent radical nephrectomy + left hemicolectomy under general anesthesia, and postoperative pathology confirmed the diagnosis of renal malacoplakia, which involved the mucosa of the intestinal tube and the entire muscular layer. The patient was followed up for 6 months after surgery, and no recurrence was seen on CT.

Hemangioma of the penile head is rare. This paper reported a patient, 16 years old, who was admitted to hospital due to the discovery of multiple masses on the head of the penis for more than two years. Physical examination showed that three vascular mass-like masses were distributed along the coronal sulcus at the 3, 9, and 12 points of the penile head, and the larger one was about 10 mm×5 mm size, blue-purple, soft, and painless. Ultrasound examination suggested that the patient had a penile head hemangioma. Surgical resection was performed, and the postoperative pathological diagnosis was penile head hemangioma.The follow-up of 3 months showed that the wound healed well without recurrence, and the penile head appearance was not obviously deform.

Objective To investigate the efficacy of transcranial direct current stimulation(tDCS)on sleep disorder in patients with Parkinson's disease(PD).Methods From July 2021 to July 2023,patients with PD and sleep disorders in the Department of Neurosurgery of the Second People's Hospital of Guangdong Province were selected.The enrolled patients were divided into sham stimulation group(n=28)and true stimulation group(tDCS)(n=29)according to the inclusion and exclusion criteria.MDS-UPDRS,PDSS and other rating scales were used to evaluate the patients.Before and after tDCS treatment,MS-11 was used for intelligent sleep monitor-ing.The baseline and improvement of sleep disorders in the two groups before and after treatment were analyzed.Results Before tDCS treatment,there was no significant difference in general conditions and scale scores between the two groups(P＞0.05).There was no significant difference in polysomnographic monitoring results between the two groups before treatment(P＞0.05).Compared with pre-treatment,there was no significant difference in sleep monitoring results in the sham stimulation group(P＞0.05),while the sleep duration and sleep efficiency signifi-cantly increased,the nighttime awakening duration,nighttime awakening frequency,MDS-UPDRS-Ⅲ score,and LEDD dose significantly decreased in the true stimulation group,with statistical significance(P＜0.05).Conclusion Pharmacological treatment combined with tDCS treatment is effective for sleep disorders and motor function in patients with PD,which could increase the sleep duration and sleep efficiency of PD patients with sleep disorders to a certain extent,reduce the nighttime awakening duration and frequency,thereby improving the fatigue symp-toms during the daytime,and improving the efficacy of conventional pharmacological treatment for PD.

The treatment of inner ear disease is developing towards local drug delivery to avoid drawbacks of systemic approach.The cochlear implants with drug delivery functions,a newly developed method of drug delivery into inner ear for treatment,has become the focus of research in recent years.In this review,we will describe recent advances in characteristics,product developments and applications of different types of drug loaded cochlear implants for local therapy.

【Objective】 To investigate whether diosmetin has protective effects on renal ischemia-reperfusion (I/R) injury in mice and explore the potential mechanism. 【Methods】 A total of 45 BALB/c male mice were randomly divided into the sham group, I/R group and diosmetin treatment group. The protective effects of diosmetin on the renal function of mice was evaluated by detecting blood biochemical indexes and renal tissue HE staining injury score. The expression of p-P65, a key molecule of NF-κB family, was detected with immunohistochemistry and western blotting, and the downstream inflammatory factors of NF-κB signaling pathway were detected with quantitative polymerace chain reaction (qPCR). 【Results】 Compared with the sham group, the I/R group had significantly increased levels of serum creatinine and urea nitrogen, significantly damaged morphological construction, and significantly increased expressions of p-P65 and inflammatory cytokines, while the diosmetin treatment group had decreased levels of serological indexes, improved structure of kidney tissue and reduced expressions of p-P65 and inflammatory cytokines. 【Conclusion】 Diosmetin can protect kidney from I/R-induced acute kidney injury by inhibiting NF-κB pathway in mice.

β-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring β-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better β-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters K_m, V_max and K_cat/K_m were 0.81 mmol, 291.99 μmol/(mg·min), and 387.50 s^-1 mmol^-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.
beta-Glucosidase ; Sodium Chloride ; Temperature ; Glucose ; Ethanol/chemistry* ; Ions ; Hydrogen-Ion Concentration ; Enzyme Stability ; Substrate Specificity

Objective:To compare the efficacy and safety of programmed death-1(PD-1)inhibitors in combination with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer.Methods:A retrospective analysis was performed on the clinical data of 77 cases of metastatic bladder cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2022. According to the different clinical treatment regimens, they were divided into two groups. Patients treated with PD-1 inhibitors combined with gemcitabine and cisplatin (GC) regimen were referred to as IGC group, and patients who received GC chemotherapy alone were referred to as GC group. There were 24 cases in IGC group, including 18 males and 6 females, with a median age of 60 (56, 67) years old. Seventeen cases had a history of smoking. Fifteen cases had an Eastern Cooperative Oncology Group (ECOG) score of 0 and 9 cases had a score of 1. Twenty-three cases suffered distant metastasis (stage M 1). Two cases suffered lymph node metastasis only, 6 cases with liver metastasis, 8 cases with lung metastasis, and 8 cases with bone metastasis. There were 53 cases in GC group, including 45 males and 8 females, with a median age of 63 (55, 69) years old. Thirty-one cases had a history of smoking. Thirty cases had an ECOG score of 0 and 23 cases had a score of 1, 48 cases suffered stage M 1, 2 cases suffered lymph node metastasis only. Nineteen cases suffered liver metastasis. Twenty-seven cases suffered lung metastasis. And 23 cases suffered bone metastasis. There was no statistically significant difference in the above general information between the two groups ( P>0.05). Kaplan-Meier method was used to plot the survival curves, and the difference of median progression-free survival (mPFS) and median overall survival (mOS) between the two groups was compared by log-rank test. Finally, the difference in adverse reactions between the two groups was compared. Results:The objective response rate (ORR) was 41.7% and the disease control rate (DCR) was 87.5% in the IGC group.As a comparison, the ORR was 43.4% and the DCR was 83.0% in the GC group. The differences in ORR ( P=0.887) and DCR ( P=0.871) between the two groups were not statistically significant. All patients were followed up for 3 to 45 months, with a median follow-up time of 24 (14, 43) months. The mPFS was 7.0 (95% CI 5.7-8.3) months in the GC group and 8.0 (95% CI 3.0-13.1) months in the IGC group, and the difference was statistically significant between the two groups ( P=0.026). The mOS of patients in the GC group was 16.0 (95% CI 14.4-17.6) months, the mOS was not yet reached in the IGC group, and patients in the IGC group had longer mOS with a statistically significant difference ( P=0.022). All patients experienced treatment-related adverse reactions. Grade 3-4 adverse reactions occurred in 8 cases (33.3%) in the IGC group and in 16 cases (30.2%) in the GC group, and no adverse reaction-related deaths were observed( P=0.992). The most common adverse reactions in both groups were anemia, including 18 cases (75.0%) in IGC group and 38 cases (71.7%) in GC group. There were 4 cases (16.7%) of grade 1-2 hypothyroidism in the IGC group but no patients with hypothyroidism were found in the GC group, and the difference was statistically significant ( P=0.012). There were 8 cases (33.3%) and 4 cases (7.5%) of grade 1-2 skin adverse reactions in the IGC and GC groups, respectively, and the difference was statistically significant ( P=0.011). The immune-related adverse reactions of PD-1 inhibitors in IGC group were 1 case of hyperthyroidism (4.2%), 4 cases of hypothyroidism (16.7%), 1 case of adrenal insufficiency (4.2%), and 1 case of immune colitis (4.2%). Conclusions:Compared with chemotherapy alone, PD-1 inhibitors combined with chemotherapy for metastatic bladder cancer can effectively prolong the mPFS and median mOS. The adverse reactions of the two groups were tolerable, and there was no significant difference in the incidence of grade 3-4 adverse reactions. In general, PD-1 inhibitors combined with chemotherapy in the treatment of metastatic bladder cancer is safe and feasible, but attention should be paid to the immune-related adverse reactions of PD-1 inhibitors.

Carbonic anhydrase IX (CAIX) is a transmembrane protein that is specifically overexpressed on the surface of hypoxic tumor cells. With the function of regulating the acidity of tumor cells both inside and outside, CAIX is closely related to tumor proliferation, invasion and metastasis. Therefore, CAIX is a promising target for tumor imaging and therapy. Herein, we summarized recent advances in CAIX-based tumor imaging, therapy and theranostics, and prospected future applications of using CAIX as an anti-tumor target.
Carbonic Anhydrase IX ; Carbonic Anhydrases/metabolism* ; Cell Line, Tumor