The Toxicity Differences of Fluralaner against the Red Imported Fire Ant (Solenopsis invicta) at Different Developmental Stages.

The red imported fire ant (RIFA), Solenopsis invicta, is an invasive pest that causes damage to agricultural and ecological environments worldwide. Fluralaner is a new isoxazoline pesticide with the potential to become a control agent against RIFA. However, it is not clear whether S. invicta responds the same way to fluralaner at different reproductive stages. The present study firstly evaluated the toxicity of fluralaner to S. invicta at different developmental stages, finding that fourth instar larvae (LD50, 1744.23 mg/kg) and worker ants (LD50, 8.62 mg/kg) were differently susceptible to fluralaner, while the mortality rate of fourth instar larvae was significantly lower at the same concentration of 10 mg/L (5.56 ± 3.14%) than that of worker ants (62.22 ± 3.14%), demonstrating a greater tolerance to fluralaner. Subsequently, the metabolic responses of worker and larval ants to fluralaner stress (10 mg/L) were investigated using non-targeted metabolomics, which indicated that the amount of differential metabolites and the KEGG metabolic pathways enriched were different between workers and larvae when exposed to the same dose (10 mg/L) of fluralaner. Differential metabolites of larvae and worker ants under fluralaner stress were mainly concentrated in organic acids and their derivatives, lipids and lipid-like molecules, nucleosides, nucleotides, and analogues, combined with the enriched metabolic pathways, revealed that the differential metabolic responses of larvae and worker ants were mainly in energy metabolism, detoxification metabolism, and neurotransmitter ligands. Workers consumed more substrates in the arginine synthesis pathway (l-glutamic acid, l-aspartic acid, and fumaric acid) to provide energy for the detoxification (glutathione) of pesticides when exposed to fluralaner stress, and the high accumulation of l-aspartic acid induced excitotoxicity in the worker ants. Larval ants consumed more arachidonic acid to synthesize PG D2, and changes in the metabolism of antioxidants such as catechins, hesperidin, and l-ascorbic acid suggested that larvae were more capable of scavenging the ROS response than worker ants. The results of non-targeted metabolomics successfully revealed differences in the sensitivity of larvae and workers to fluralaner agents, providing insights into the fluralaner control of Solenopsis invicta.

EDL structure of ionic liquid-MXene-based supercapacitor and hydrogen bond role on the interface: a molecular dynamics simulation investigation.

As a new class of electrodes, MXenes have shown excellent performance in supercapacitors. At the same time, ionic liquid (IL) electrolytes with wider electrochemical windows are expected to substantially increase the supercapacitor capacitance. The combination of MXenes and ILs is promising for energy storage devices with a high energy density and power density. The studies have indicated that the surface terminations of MXenes and the functional groups of ILs, can both strongly influence the supercapacitor's performance. However, studies at the molecular level are still lacking. In this work, we performed molecular dynamics simulations to investigate the interfacial structures and their influence on the energy storage mechanism. The results show that the two ILs exhibit very different charging rates, though the charge densities are similar after charging equilibrium. The interfacial analysis reveals different electrical double-layer (EDL) structures, in which most cations stay perpendicular to the Ti3C2(OH)2 electrode when some cations shift to a vertical arrangement near the Ti3C2O2 electrode. Such structures have led to the higher capacitance of the Ti3C2(OH)2 electrode, even more than 2 times that of the Ti3C2O2 electrode as the potential difference ranges from 0 to 2 V. It was also found that hydrogen bonds between the -OH groups of HEMIm+ cations and terminations of the MXene play an important role in improving the capacitances by aggregating more HEMIm+ cations on the surface of the Ti3C2(OH)2 electrode. Our work provides clear mechanistic evidence that both terminations of the MXene electrodes and functional groups of the IL electrolytes affect the interfacial structures and the EDL formation, further leading to the different supercapacitor performance, which will be helpful in designing highly efficient energy-storage devices.

Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa.

BACKGROUND: Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as Mycobacterium smegmatis and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as Saccharomyces cerevisiae. RESULTS: Two EGT biosynthetic genes were cloned from the mushroom Grifola frondosa and successfully heterologously expressed in Saccharomyces cerevisiae EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain S. cerevisiae EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain S. cerevisiae EC1118 can reach up to 20.61 mg/L. CONCLUSION: A successful EGT de novo biosynthetic system of S. cerevisiae containing only two genes from mushroom Grifola frondosa was developed in this study. This system provides promising prospects for the large scales production of EGT for human health.

SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors.

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating from the liver. These tumors are associated with heterogeneous prognosis, and few treatment targets for PHNETs have been identified. Because the major genetic alterations in PHNET are still largely unknown, we performed whole-exome sequencing of 22 paired tissues from PHNET patients and identified 22 recurring mutations of somatic genes involved in the following activities: epigenetic modification (BPTF, MECP2 and WDR5), cell cycle (TP53, ATM, MED12, DIDO1 and ATAD5) and neural development (UBR4, MEN1, GLUL and GIGYF2). Here, we show that TP53 and the SET domain containing the 1B gene (SETD1B) are the most frequently mutated genes in this set of samples (3/22 subjects, 13.6%). A biological analysis suggests that one of the three SETD1B mutants, A1054del, promotes cell proliferation, migration and invasion compared to wild-type SETD1B. Our work unveils that SETD1B A1054del mutant is functional in PHNET and implicates genes including TP53 in the disease. Our findings thus characterize the mutational landscapes of PHNET and implicate novel gene mutations linked to PHNET pathogenesis and potential therapeutic targets.

Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.

To explore the effects of IL-7/IL-7R on the RANKL-mediated osteoclast differentiation in vitro and OVX-induced bone loss in vivo. BMMs and RAW264.7 were transfected with IL-7, IL-7R siRNA, c-Fos siRNA, and c-jun siRNA and later stimulated by RANKL. TRAP and toluidine blue staining were used to observe osteoclast formation and bone resorption, respectively. HE and TRAP staining were used to detect trabecular bone microstructure and osteoclasts of mice, respectively. qRT-PCR and Western blot analysis were used to examine expression. IL-7 unregulated the expression of CTSK, NFATc1, MMP9, and the phosphorylation of p38 and Akt by activating the c-Fos/c-Jun pathway, which increased osteoclast numbers and bone resorption in RANKL-stimulated macrophages. While IL-7R siRNA and c-Fos siRNA decreased the expression, as well as and the phosphorylation of p38 and Akt.IL-7 decreased the BMD and OPG expression in OVX-induced mice and increased the TRAP positive cells, the mRNA expression of c-fos, c-jun, and RANKL, which was contradictory to IL-7R siRNA, and c-Fos siRNA. Furthermore, IL-7R siRNA and c-Fos siRNA caused thicker trabeculae, increased trabecular number, and decreased osteolysis in OVX mice. IL-7/IL-7R can promote RANKL-mediated osteoclast formation and bone resorption by activating the c-Fos/c-Jun pathway, as well as inducing bone loss in OVX mice.

Surface Decorated Porphyrinic Nanoscale Metal-Organic Framework for Photodynamic Therapy.

Nanocrystallization of organic molecular photosensitizers (PSs) by means of NMOF platforms has been demonstrated to be a promising approach to build up highly efficient PDT therapeutics. We report herein a new UiO-66 type of NMOF-based PS (UiO-66-TPP-SH), which is generated from UiO-66 NMOF and S-ethylthiol ester monosubstituted metal free porphyrin (TPP-SH) via a facile postsynthetic approach under mild conditions. The obtained NMOF (size less than 150 nm) with surface-decorated porphyrinic PS can not only retain MOF crystallinity, structural feature, and size, but also exhibit highly efficient singlet oxygen generation. Compared to the interior-located porphyrinic NMOF, UiO-66-TPP-SH shows significantly higher photodynamic activity and more efficient PDT tumor treatment.

Single Nucleotide Polymorphism of the Enhancer of Zeste Homolog 2 Gene rs2072408 is Associated with Lymph Node Metastasis and Depth of Primary Tumor Invasion in Gastric Cancer.

BACKGROUND: The single nucleotide polymorphism (SNP) rs2072408 is located in an intron of the enhancer of zeste homolog 2 (EZH2) gene. Its role in gastric cancer (GC) has not been determined. METHODS: In the present study, the genotype of (EZH2) rs2072408 and the relationship of genotype with lymph node metastasis (LNM) and the invasive depth of gastric wall (T stage) was determined in 330 patients with GC, and the association between the genotype and recurrence and survival was determined in 253 patients with GC. RESULTS: The TT genotype was identified to be significantly associated with LNM [P = 0.013; odds ratio (OR), 6.49 (95% confidence interval (CI), 1.47 - 28.59)] and T stage [T1 + T2 vs. T3 + T4, p = 0.017, OR, 3.02 (95% CI, 1.22 - 7.44)]. The overall rates of LNM and T3 + T4 stage in the present study were 70.6% and 60.6%, respectively, the rates increased 23.8% and 20.0% in patients with the TT genotype. CONCLUSIONS: These results suggest that the TT genotype of EZH2 (rs2072408) was associated with LNM and the depth of gastric wall invasion in patients with GC.

The Value of Preoperative Neutrophil to Lymphocyte Ratio in Indicating Lymph Node Metastasis in Patients with Resectable T2 Stage Gastric Adenocarcinoma.

BACKGROUND: Lymph node metastasis (LNM) is closely associated with poor prognosis in patients with resectable T2 stage gastric adenocarcinoma (RT2-GA). Preoperative blood neutrophil to lymphocyte ratio (NLR) has been identified to be a very valuable predictor for prognosis in patients with diverse cancers. The aim of this investigation was to assess the relationship between NLR and LNM in RT2-GA. METHODS: This retrospective study reviewed 230 patients who underwent surgery for removal of primary T2-GA from August 2002 to December 2013 in a single hospital. Preoperative routine blood test data were collected and the relationship between NLR and LNM in RT2-GA was evaluated by X2 test and multivariate logistic regression analysis. RESULTS: The median value of NLR was 2.18 among 230 patients. Based on the median NLR value, the patients were categorized into two groups: low NLR group (NLR ≤ 2.18) and high NLR group (NLR > 2.18). χ2 test results exhibited that the preoperative NLR was significantly associated with the numbers of metastatic lymph nodes (≤ 6 and > 6) (p = 0.003) and status of lymph node involvement (N0, N1, and N2 stage) (p = 0.032). Multivariate analyses further confirmed that NLR > 2.18 was significantly associated with increased risk of appearing more numbers of metastatic lymph node or higher N stage which exhibited a 4.15- or 7.09-fold elevated risk compared to that of NLR ≤ 2.18. CONCLUSIONS: The preoperative NLR is closely associated with LNM in patients with RT2-GA, which may be used as a predictor indicating more serious LNM in this type of cancer.

SNP rs1059234 in CDKN1A Gene Correlates with Prognosis in Resected Gastric Adenocarcinoma.

BACKGROUND: Cyclin-dependent kinase inhibitor 1A (CDKN1A) and Cyclin D1 (CCND1) play essential roles in the regulation of cell cycle progression and are closely associated with human cancer. CDKN1A and CCND1 single nucleotide polymorphisms (SNPs) have been demonstrated to influence the prognosis in humans with different cancers. However, their roles in the prognosis of patients with resected gastric adenocarcinoma (RGA) remain to be determined. METHODS: Genotypes of CDKN1A rs1059234 and CCND1 rs603965 SNPs were performed in 235 tissue samples from RGA. The association of the genotypes of these two SNPs with the prognosis in the patients with RGA was analyzed by X2 test, multivariate Cox regression analyses, and Kaplan Meier curves. RESULTS: During the 50 months of median follow-up time, the overall recurrence and survival rate in the whole group was 57.4% and 46.8%, respectively. Whereas, recurrence and survival rate in patients with CC genotype of rs1059234 located in 3'UTR of CDKN1A were 78.0% and 27.1% (p = 0.004; p = 0.006). Multivariate analyses further confirmed that the CC genotype was significantly related with both increased recurrence and death risk (HR 3.33, 95% CI 1.95-5.70; p = 1.07 x 10⁻5, and HR 3.45, 95% CI 1.95-6.10; p = 2.03 x 10⁻5). No significant difference among CCND1 rs603965 SNP with the prognosis was determined. CONCLUSIONS: rs1059234 of CDKN1A is closely associated with the prognosis in patients with RGA.

Expression and clinical significance of long non-coding RNA HNF1A-AS1 in human gastric cancer.

BACKGROUND: Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play essential roles in the occurrence and development of human cancers, including gastric cancer (GC). However, the functional and clinical significance of lncRNAs are still poorly understood. METHODS: In this study, the expression of LncRNA HNF1A antisense RNA 1 (HNF1A-AS1) was first examined by lncRNAs microarray analysis in 6 GC tissues, and was then further verified by real-time quantitative reverse transcription PCR (qRT-PCR) both in 3 GC cell lines and 161 cases of GC tissues. We also evaluated the association between HNF1A-AS1 expression and clinicopathological features of patients with GC. RESULTS: LncRNAs microarray analysis results exhibited that HNF1A-AS1 was downregulated in GCs tissues (mean fold change 2.06, p < 0.05), which was further confirmed by qRT-PCR. The results from qRT-PCR showed that the expression of HNF1A-AS1 was not only downregulated in three GC cell lines (AGS, BGC-823, and MKN-45) relative to that in a normal gastric mucosal epithelial cell line (GES-1), but also decreased in GC tissues relative to that in paired adjacent non-neoplastic tissues (low expression, 94 of 161; low expression rate, 58.38%). Furthermore, low HNF1A-AS1 expression was associated with tumor size/diameter (p = 0.005, multivariate analysis), levels of serum carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), and RRM1 expression in tissue samples (p = 0.028, p = 0.009, and p = 0.006, respectively). CONCLUSIONS: Taken together, our data indicate that lncRNA HNF1A-AS1 may be a regulator of GC, and thus, it may have potential as a novel biomarker and treatment target for this type of cancer.

IL-1ß-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9.

BACKGROUND: Interleukin-1ß (IL-1ß) has been implicated in the progression of gastric adenocarcinoma (GA); however, the molecular mechanisms of action of IL-1ß in GA are poorly characterized. P38 and JNK are the major MAPK family members that regulate IL-1ß signaling pathways. Here, we investigated the role of both p38 and JNK in IL-1ß-induced GA cell migration, invasion and metastatic potential. METHODS: The effects of IL-1ß-induced p38 and JNK activation in GA cells were determined using in vitro Transwell migration and invasion assays of MKN-45 and AGS cells, or an in vivo metastasis assay in nude mice. The IL-1ß-induced p38 signaling pathway was further characterized in GA cells. Activation of the IL-1ß/p38 signaling pathway was also assessed in human primary GA tissues by immunohistochemistry. RESULTS: IL-1ß-induced activation of p38 increased GA cell migration and invasion in vitro and promoted the metastatic potential of GA cells in vivo; these effects were attenuated by p38 siRNA or the p38 inhibitor SB202190. MMP2 or MMP9 siRNAs and the MMP2/9 inhibitor BiPS also inhibited IL-1ß-induced GA cell migration and invasion in vitro. IL-1ß-induced p38 activation significantly increased MMP2 and MMP9 mRNA and protein expression and activity. Luciferase reporter assays demonstrated that the activator protein-1 (AP-1) and the AP-1 binding sites of the MMP9 promoter (-670/MMP9) were activated by IL-1ß-induced p38 activation. Phospho-p38 was significantly upregulated in human GA tissues (compared to matched non-neoplastic tissues), and significantly associated with lymph node metastasis, and invasion beyond the serosa. Expression of phospho-p38 significantly correlated with IL-1ß, MMP2, MMP9, and c-fos expression in both human GA tissues and GA cell metastases in the lungs of nude mice. IL-1ß was also capable of activating JNK in GA cells, but activation of JNK was not associated with GA cell migration and invasion. Therefore, IL-1ß-induced the migration and invasion in GA cells were regulated by p38, but not by JNK. CONCLUSIONS: IL-1ß-induced p38 activation and the IL-1ß/p38/AP-1(c-fos)/MMP2 & MMP9 pathway play an important role in metastasis in GA; this pathway may provide a novel therapeutic target for GA.

[A clinical analysis of eight proven cases of pulmonary mucormycosis].

OBJECTIVE: To improve the understanding of pulmonary mucormycosis by analyzing the clinical manifestations, imaging features, diagnosis, treatment and prognosis of this disease. METHODS: The clinical data of eight patients diagnosed as pulmonary mucormycosis by histopathologic examination were retrospectively analyzed. RESULTS: Eight patients included six males and two females with age from 36 days to 66 years. Underlying conditions covered diabetes (n = 4), renal transplantation (n = 3), premature (n = 1) and long-term corticosteroid treatment in two cases. Imaging manifestations revealed multiple irregular lumps or nodules in three cases, multiple cavities with thick wall in three cases, diffuse lung infiltrate in one case and lung opacities in one case. The diagnoses of seven patients were confirmed by percutaneous needle lung biopsy and the remaining one was diagnosed with fiberoptic bronchoscopy biopsy. Surgery combined with amphotericin B liposome (60 mg/d for three weeks) was applied to one patient who was cured with no recurrence after a 22 month follow-up. Three cases were given amphotericin B liposome (a newborn with 7mg/d for 62 days, the other two 60 mg/d for 31 days and 70 mg/d for 71 days respectively). All had achieved marked response with follow up from 8 to 29 months, but one patient relapsed and died of recurrent lung mucormycosis. The other three patients were treated with itraconazole 400-200 mg/d from 21 days to 1 year with duration of follow up from 1 month to 20 months. One patient was not evaluable due to missing. Two patients relapsed and one died. CONCLUSION: Pulmonary mucormycosis is difficult to diagnose and treat with a high mortality. Percutaneous transthoracic lung biopsy is a useful diagnostic method. Amphotericin B liposome or itraconazole may be active against mucus. Early control of causes is essential to improve the prognosis and reduce the recurrence in patients with pulmonary mucormycosis.

External fixator versus Ilizarov external fixator for pediatric tibial shaft fractures: A retrospective comparative study.

INTRODUCTION: External fixators (EF) are widely employed for pediatric tibial shaft fractures, being a prevalent choice in clinical practice. However, they are associated with numerous complications, such as loss of reduction, delayed union, and nonunion. An alternative approach involves the use of Ilizarov external fixators (IEF), which have been documented in the treatment of tibial shaft fractures in various studies. This study endeavors to retrospectively compare the clinical outcomes of EF and IEF in the treatment of pediatric tibial shaft fractures. METHODS: The study retrospectively examined patients aged 5-14 years who underwent treatment for tibial shaft fractures at our institute between January 2017 and January 2023. These individuals were subsequently classified into EF and IEF groups. Exclusions comprised patients presenting with pathological fracture, neuromuscular disorder, metabolic disease, prior tibial fracture or instrumentation, and polytrauma. Additionally, individuals with a follow-up duration of more than 12 months or incomplete medical records were excluded. RESULTS: A total of 45 patients were divided into two groups: the EF group, comprising 24 patients (18 males, 6 females), and the IEF group, consisting of 21 patients (17 males, 4 females). The two groups exhibited no statistically significant differences in terms of sex, age, body weight, time from injury to surgery, AO classification, or concomitant injuries. There were two cases of nonunion in the EF group. Radiological union occurred more rapidly in the IEF group (7.8 ± 0.4 weeks) than in the EF group (9.3 ± 1.1 weeks) (P < 0.05). The mean hospitalization duration differed significantly between the EF group (6.7 ± 3.4 days) and the IEF group (7.5 ± 1.1 days) (P > 0.05). The mean duration of the operative procedure significantly differed between the IEF group (147.8 ± 24.5 min) and the EF group (77.2 ± 43.9 min) (P < 0.001). A significant difference (P < 0.001) in weight-bearing time was observed between the IEF group (2.6 ± 0.7 weeks) and the EF group (9.9 ± 1.4 weeks). According to the Johner-Wruhs criteria, no significant differences were found between the two groups. A significant difference (P < 0.001) in hospitalization costs was observed between the IEF group (7848.0 ± 262.4 $) and the EF group (5403.0 ± 233.3 $). CONCLUSION: EF is cheaper, quicker and simpler and we need more randomized controlled studies and that this is a pilot study only. Both types of surgery are good choices for children. Nevertheless, the IEF group demonstrates advantages such as early weight-bearing capability and faster fracture healing.

A 3D-printed phantom for stereotactic body radiation therapy simulation.

In modern radiation therapy for lung cancer, examining the uncertainty between tumor motion and beam delivery is vitally important. To lower the radiation dose delivery to the patient's normal tissue, narrowing the irradiation field margin to hit the tumor accurately is critical. Thus we proposed a phantom that simulates the thorax and lung tumor's motions by employing a 3D printing technique. The lung tumor is controlled by a linear miniature Delta robot arm, with a maximum displacement of 20 mm in each direction. When we simulated the thoracic breathing movements at 12 mm in A-P (Anterior-Posterior), the control errors were within 10%. The average tracking errors of the prosthetic tumor were within 1.1 mm. Therefore, the 3D-printed phantom with a robot arm can provide a reliable simulation for training and dosimetry measurement before lung radiotherapy, especially SBRT.

Invasive cancers are not necessarily from preformed in situ tumours - an alternative way of carcinogenesis from misplaced stem cells.

Cancers are thought to be the result of accumulated gene mutations in cells. Carcinomas, which are cancers arising from epithelial tissues usually go through several stages of development: atypical hyperplasia, carcinoma in situ and then invasive carcinoma, which might further metastasize. However, we think that the present pathological data are enough to prove that there might be an alternative way of carcinogenesis. We propose that majority of invasive cancers arise in the connective tissue stroma de novo, from the misplaced epithelial stem cells which come to the wrong land of connective tissue stroma by accident. The in situ carcinomas, which are mostly curable, should not be considered genuine cancer, but rather as quasi-cancer. We design this new theory of carcinogenesis as the stem cell misplacement theory (SCMT). Our SCMT theory chains together other carcinogenesis theories such as the inflammation-cancer chain, the stem cell theory and the tissue organization field theory. However, we deny the pathway of somatic mutation theory as the major pathway of carcinogenesis.

Clinicopathologic features and long-term prognosis of hepatitis B virus-associated glomerulonephritis: a retrospective cohort study.

BACKGROUND: Hepatitis B virus-associated glomerulonephritis is a common form of secondary glomerulonephritis in China. However, the clinicopathological features and long-term prognosis of Hepatitis B virus-associated Glomerulonephritis remain only partially known. METHODS: Biopsy-proven Hepatitis B virus-associated Glomerulonephritis patients were enrolled between November 1994 and December 2013 at our center. The composite endpoints were doubling serum creatinine, end-stage renal disease, or death from renal disease during follow-up. The clinicopathological features and predictors of the long-term prognosis of Hepatitis B virus-associated Glomerulonephritis patients were explored. RESULTS: The median age of the 259 Hepatitis B virus-associated Glomerulonephritis patients was 31.0 years (IQR 24.0-40.0), and 71.0% were males. Among the patients, 45.2% presented with nephrotic syndrome, and 45.9% presented with proteinuria combined with hematuria. The two most prevalent pathological patterns were IgA nephropathy (27.0%) and membranous nephropathy (27.0%). The mean follow-up period was 68.8 ± 46.9 months. The 3-, 5-, and 10-year clinical event-free survival rates were 93.4%, 85.2%, and 70.3%, respectively. Multivariable Cox regression analysis showed that hypertension (HR 2.580, 95% CI 1.351-4.927, P = 0.004), hyperuricemia (HR 2.101, 95% CI 1.116-3.954, P = 0.021), glomerulosclerosis (P = 0.001), and intrarenal arterial lesions (P = 0.041) were independent predictors of composite clinical event endpoint. Patients in the antiviral therapy group exhibited a significantly better prognosis compared to those who received no antiviral therapy (log-rank χ2 = 5.772, P = 0.016). CONCLUSION: Hepatitis B virus-associated Glomerulonephritis has specific clinicopathologic features and should not be considered a benign disease in adults. Hypertension, hyperuricemia, glomerulosclerosis, and intrarenal arterial lesions were independent predictors of the long-term prognosis in Hepatitis B virus-associated Glomerulonephritis patients. Antiviral therapy could be effective in improving the long-term prognosis of Hepatitis B virus-associated Glomerulonephritis patients.

Ganoderma Fusions with High Yield of Ergothioneine and Comparative Analysis of Its Genomics.

Ergothioneine (EGT), an exceptional antioxidant found ubiquitously across diverse living organisms, plays a pivotal role in various vital physiological regulatory functions. Its principal natural sources are mushrooms and animal liver tissues. Ganoderma spp., a traditional Chinese food and medicinal mushroom, boasts high concentrations of EGT. To advance the development of novel Ganoderma spp. strains with enhanced EGT yields, we employed an efficient Ganoderma spp. protoplasmic fusion system. Through molecular and biological characterization, we successfully generated seven novel fusion strains. Notably, fusion strain RS7 demonstrated a remarkable increase in mycelial EGT production (12.70 ± 1.85 mg/L), surpassing the parental strains FQ16 and FQ23 by 34.23% and 39.10%, respectively. Furthermore, in the context of the fruiting body, fusion strain RS11 displayed a notable 53.58% enhancement in EGT production (11.24 ± 1.96 mg/L) compared to its parental strains. Genomic analysis of the RS7, the strain with the highest levels of mycelial EGT production, revealed mutations in the gene EVM0005141 associated with EGT metabolism. These mutations led to a reduction in non-productive shunts, subsequently redirecting more substrate towards the EGT synthesis pathway. This redirection significantly boosted EGT production in the RS7 strain. The insights gained from this study provide valuable guidance for the commercial-scale production of EGT and the selective breeding of Ganoderma spp. strains.

HER-2/neu overexpression is an independent prognostic factor for intestinal-type and early-stage gastric cancer patients.

GOALS: To evaluate the HER-2/neu protein level by immunohistochemistry (IHC) and its gene amplification by fluorescence in situ hybridization (FISH) in gastric cancer samples, and the relevance to the prognosis of gastric cancer patients. STUDY: HER-2/neu overexpression and gene amplification were examined with semiquantitative standardized IHC in 775 formalin-fixed paraffin-embedded gastric cancer samples, and 252 of these cases were analyzed with FISH. RESULTS: Of the 775 gastric cancer samples examined by IHC, a total of 88 (11%) cases were positive for HER-2/neu overexpression at a score of 3+; another 44 (6%) cases were equivocal with a score of 2+; and the rest 643 (83%) cases were negative scored as 0/1+. Intestinal-type and early-stage cancers exhibited higher rate of HER-2/neu overexpression than those of diffuse/mixed-type and advanced cancers (P<0.05). Intestinal-type and early-stage cancers with HER-2/neu overexpression also exhibited short 5 year survival rates (21% vs. 47%, P=0.027; 29% vs. 60%, P=0.037) than HER-2/neu-negative cases, but not in the diffuse/mixed-type and advanced stage cancers. By FISH analysis, it was shown that 70% (60/86) of IHC 3+ had HER-2/neu gene amplication. In contrast, only 14% (6/43) of IHC 2+ cases, and 2.5% (3) of the 120 cases with IHC 0/1+ randomly selected showed HER-2/neu gene amplification. CONCLUSIONS: HER-2/neu overexpression may be used as an independent prognostic factor for intestinal-type and early-stage gastric cancer patients. IHC 3+ and 2+ cases should be further detected by FISH to assess HER-2/neu gene status. Patients with HER-2/neu amplification also might constitute potential candidates for targeted therapy with trastuzumab.

Synthesis of CuO/GO-DE Catalyst and Its Catalytic Properties and Mechanism on Ciprofloxacin Degradation.

A new catalyst, copper oxide/graphene oxide-diatomaceous earth (CuO/GO-DE), was prepared by the ultrasonic impregnation method. The optimal conditions for catalyst preparation were explored, and its structure and morphology were characterized by BET, XRD, SEM, TEM, FTIR, Raman and XPS. By taking ciprofloxacin as the target pollutant, the performance and reusability of CuO/GO-DE to degrade antibiotic wastewater was evaluated, and the optimal operating conditions were obtained. The main oxidizing substances in the catalytic system under different pH conditions were analyzed, as well as the synergistic catalytic oxidation mechanism. The intermediate products of ciprofloxacin degradation were identified by LC-MS, and the possible degradation process of ciprofloxacin was proposed.

[The expression and significance of nephrin in hepatitis B virus-associated membranous nephropathy].

OBJECTIVE: To observe the expression of nephrin in hepatitis B virus-associated membranous nephropathy (HBV-MN), and investigate the impairment and significance of podocyte in HBV-MN. METHODS: The protein expression of nephrin in renal biopsy specimens in 35 patients, who were diagnosed as HBV-MN by renal biopsy, was determined by immunohistochemistry and tested by semi-quantitative method. The relationship between the expression of nephrin and clinicopathological data was analyzed. RESULTS: Among the 35 cases with HBV-MN, 6 were in MN phase I, 20 in MN phase II and 9 in MN phase III. A strong intensity expression of nephrin in normal glomerulus was found along capillary loop of glomerulus, while its expression in HBV-MN patients decreased obviously. There was no significantly difference in the expression of nephrin among the different stages of HBV-MN (P > 0.05). The expression of nephrin in different clinical types was significantly different(P < 0.05). The expression of nephrin in patients with nephrotic syndrome was significantly lower than that in patients without nephrotic syndrome (P < 0.01). The expression of nephrin in different grades of 24-hour urinary protein excretion quantity was significantly different(P < 0.05). There was negative correlation between the expression of nephrin and 24-hour urinary protein excretion quantity(r = -0.378, P < 0.05). In the patients with HBV-MN phase II, the expression of nephrin in patients with nephrotic syndrome was also significantly lower than that in patients without nephrotic syndrome (P < 0.01). CONCLUSIONS: The damage of podocytes emerge in the early stage of HBV-MN and the expression of nephrin in HBV-MN patients, especially in patients with nephrotic syndrome, are significantly down regulated. The descended expression of nephrin in HBV-MN patients may promote the production of proteinuria.