Biocompatible and Biodegradable 3D Graphene/Collagen Fiber Hybrids for High-Performance Conductive Networks and Sensors.

Polymer-based flexible conductive materials are crucial for wearable electronics, electronic skin, and other smart materials. However, their development and commercial applications have been hampered by the lack of strain tolerance in the conductive network, poor bonding with polymers, discomfort during wear, and a lack of biocompatibility. This study utilized oil-tanned leather with a natural network structure, high toughness, and high tensile deformation recovery as a structural template. A graphene (Gr) conductive network was then constructed on the collagen network of the leather, with coordination cross-linking between Gr and collagen fibers through aluminum ions (Al3+). A new flexible conductive material (Al-GL) was then constructed. Molecular dynamics simulations and experimental validation revealed the existence of physical adsorption, hydrogen bonding adsorption, and ligand bonding between Al3+, Gr, and collagen fibers. Although we established that the binding sites between Al3+ and collagen fibers were primarily on carboxyl groups (-COOH), the mechanism of chemical bonding between Gr and collagen fibers remains unclear. The Al-GL composite exhibited a high shrinkage temperature (67.4 °C) and low electrical resistance (16.1 kΩ·sq-1), as well as good softness (9.33 mN), biocompatibility, biodegradability (<60 h), and air and moisture permeability. Furthermore, the incorporation of Al3+ resulted in a heightened Gr binding strength on Al-GL, and the resistance remained comparable following 1 h of water washing. The Al-GL sensor prepared by WPU encapsulation not only demonstrated highly sensitive responses to diverse motion signals of the human body but also retained a certain degree of response to external mechanical effects underwater. Additionally, the Al-GL-based triboelectric nanogenerator (Al-GL TENG) exhibited distinct response signals to different materials. The Al-GL prepared by the one-pot method proposed in this study offers a novel approach to combining functional nanofillers and substrate materials, providing a theoretical foundation for collagen fiber-based flexible conductive materials.

MSC microvesicles loaded G-quadruplex-enhanced circular single-stranded DNA-9 inhibits tumor growth by targeting MDSCs.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors. RESULTS AND CONCLUSION: In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment.

HSP70 protects against acute pancreatitis-elicited intestinal barrier damage in rats.

Acute pancreatitis (AP) is a frequent but severe abdominal emergency in general surgery with intestinal barrier dysfunction. Heat shock protein 70 (HSP70) is a ubiquitous molecular chaperone that has been proposed to exert favorable effects on AP. Nonetheless, the detailed impacts of HSP70 on the intestinal barrier function in AP are unknown, which will be investigated here. After the injection of sodium taurocholate into the biliopancreatic duct, the rat models of AP were established. After modeling, HSP70 expression was up-regulated through lentivirus infection. Western blot was used to detect HSP70 expression. H&E staining was used to examine the histological changes in the pancreatic and intestinal tissues. The levels of pancreatic biochemical markers and oxidative stress markers were detected using corresponding assay kits. ELISA was used to detect the levels of inflammatory cytokines and gastrointestinal function indicators. Immunofluorescence staining and Western blot were used to detect the expression of tight junction proteins. DCFH-DA probe and MitoSOX Red probe were used to detect total reactive oxygen species (ROS) and mitochondrial ROS (mtROS), respectively. TUNEL assay and Western blot were used to detect apoptosis. During the model construction, severe pancreatic and abnormal intestinal tissue abnormalities were observed, inflammatory response was activated and the intestinal barrier was disrupted. HSP70 expression was down-regulated in the intestinal tissues AP rat models. HSP70 ameliorated the morphological damage of pancreatic and intestinal tissues of AP rats. In addition, HSP70 significantly reduced intestinal barrier damage, inflammatory response, oxidative stress and apoptosis in the intestinal tissues of AP rat models. Collectively, HSP70 might attenuate AP through exerting anti-inflammatory, anti-oxidant, anti-apoptotic effects and inhibiting intestinal barrier disruption.

Research advancements on the involvement of E3 ubiquitin ligase UBR5 in gastrointestinal cancers.

E3 ubiquitin ligases comprise a family of ubiquitination-catalyzing enzymes that have been extensively researched and are considered crucial components of the ubiquitin-proteasome system involved in various diseases. The ubiquitin-protein ligase E3 component n-recognition 5 (UBR5) is an E3 ubiquitin-protein ligase that has garnered considerable interest of late. Recent studies demonstrate that UBR5 undergoes high-frequency mutations, chromosomal amplification, and/or abnormalities during expression of various malignant tumors. These alterations correlate with the biological behaviors and prognoses of malignancies, such as tumor invasion, metastasis, and resistance to chemotherapeutic agents. This study aimed to comprehensively elucidate the biological functions of UBR5, and its role and relevance in the context of gastrointestinal cancers. Furthermore, this article expounds a scientific basis to explore the molecular mechanisms underlying gastrointestinal cancers and developing targeted therapeutic strategies for their remediation.

The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

Ru/Ir-Based Electrocatalysts for Oxygen Evolution Reaction in Acidic Conditions: From Mechanisms, Optimizations to Challenges.

The generation of green hydrogen by water splitting is identified as a key strategic energy technology, and proton exchange membrane water electrolysis (PEMWE) is one of the desirable technologies for converting renewable energy sources into hydrogen. However, the harsh anode environment of PEMWE and the oxygen evolution reaction (OER) involving four-electron transfer result in a large overpotential, which limits the overall efficiency of hydrogen production, and thus efficient electrocatalysts are needed to overcome the high overpotential and slow kinetic process. In recent years, noble metal-based electrocatalysts (e.g., Ru/Ir-based metal/oxide electrocatalysts) have received much attention due to their unique catalytic properties, and have already become the dominant electrocatalysts for the acidic OER process and are applied in commercial PEMWE devices. However, these noble metal-based electrocatalysts still face the thorny problem of conflicting performance and cost. In this review, first, noble metal Ru/Ir-based OER electrocatalysts are briefly classified according to their forms of existence, and the OER catalytic mechanisms are outlined. Then, the focus is on summarizing the improvement strategies of Ru/Ir-based OER electrocatalysts with respect to their activity and stability over recent years. Finally, the challenges and development prospects of noble metal-based OER electrocatalysts are discussed.

Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review.

Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is extremely rare. In this case report, a 54-year-old woman diagnosed with invasive ductal carcinoma of the left breast underwent lumpectomy, lymph node dissection, chemotherapy, and radiotherapy but opted against trastuzumab treatment. Four years later, she experienced bilateral breast inflammation, skin changes, edema, and heat (calor). Biopsies confirmed breast cancer metastasis to both breasts. Whole-Exome Sequencing revealed genetic mutations, including PIK3CA and C4orf54, in both primary and recurrent tumors, with significant downregulation in the recurrent tumors. KEGG analysis suggested potential enrichment of axon guidance signal pathways in both tumors. The patient showed a partial response after treatment with liposome paclitaxel, along with targeted therapy using trastuzumab and pertuzumab. This case report sheds light on the rare occurrence of bilateral inflammatory breast cancer post-HER-2 treatment and highlights the importance of genetic profiling in understanding the disease. Further research on clinical targets for breast cancer management is warranted.

A Bio-Inspired Free-Standing Film with Versatility: From Heterogeneous CTCs Programed Isolating to Breast Cancer Molecular Typing.

Developing a robust strategy for profiling heterogeneous circular tumor cells specifically, distinguishing the phenotypes of which in blood sample of cancer patient precisely, and releasing them sequentially, is significant for cancer management by liquid biopsy. Herein, a bio-inspired free-standing and flexible film composed of TiO2 nanotube and silk fibroin, fabricated with multiply dynamic bioactive surface (TSF/MDBS) by a simple and eco-friendly way including using polydopamine chemistry and dual dynamic covalent chemistry, is reported. The as-prepared TSF/MDBS binds specific peptides toward cells with epithelial biomarker and human epithelial growth factor receptor 2 (HER2) biomarker, and antifouling agents bovine serum albumin for obviating platelets and proteins adhering of blood, can capture heterogeneous CTCs with enhanced capability due to the cytocompatible soft film and exquisite surface design, and further release the captured cells as program, by specifically breaking down the covalent bonds in sequence via the action of adding biocompatible molecules fructose and glutathione. By applying the TSF/MDBS, it can be tailored into desired pieces for identifying CTCs with different phenotypes (HER2-high and HER2-low) from the unprocessed blood samples of breast cancer patients, and finally profiling these heterogeneous CTCs, to discriminate HER2 positive or negative of breast cancer patients in clinical applications.

Engineering Electronic Structure of Nitrogen-Carbon Sites by sp3 -Hybridized Carbon and Incorporating Chlorine to Boost Oxygen Reduction Activity.

Development of efficient and easy-to-prepare low-cost oxygen reaction electrocatalysts is essential for widespread application of rechargeable Zn-air batteries (ZABs). Herein, we mixed NaCl and ZIF-8 by simple physical milling and pyrolysis to obtain a metal-free porous electrocatalyst doped with Cl (mf-pClNC). The mf-pClNC electrocatalyst exhibits a good oxygen reduction reaction (ORR) activity (E1/2 =0.91 V vs. RHE) and high stability in alkaline electrolyte, exceeding most of the reported transition metal carbon-based electrocatalysts and being comparable to commercial Pt/C electrocatalysts. Likewise, the mf-pClNC electrocatalyst also shows state-of-the-art ORR activity and stability in acidic electrolyte. From experimental and theoretical calculations, the better ORR activity is most likely originated from the fact that the introduced Cl promotes the increase of sp3 -hybridized carbon, while the sp3 -hybridized carbon and Cl together modify the electronic structure of the N-adjacent carbons, as the active sites, while NaCl molten-salt etching provides abundant paths for the transport of electrons/protons. Furthermore, the liquid rechargeable ZAB using the mf-pClNC electrocatalyst as the cathode shows a fulfilling performance with a peak power density of 276.88 mW cm-2 . Flexible quasi-solid-state rechargeable ZAB constructed with the mf-pClNC electrocatalyst as the cathode exhibits an exciting performance both at low, high and room temperatures.

High-grade fetal adenocarcinoma of the lung misdiagnosed as male breast carcinoma: a case report and literature review.

Background and aim: High-grade fetal adenocarcinoma of the lung (HG-FLAC) is a specific subtype of lung adenocarcinoma with a poor prognosis. A lack of understanding exists because of the rarity of this disease. This study aimed to present a case of HG-FLAC with multiple metastases misdiagnosed as male breast carcinoma at the initial diagnosis. Case presentation: The patient visited our hospital due to a month-long cough. The chest computed tomography (CT) scan revealed a mass in the left lung and chest wall, accompanied by enlargement of mediastinal lymph nodes. The magnetic resonance imaging indicated potential metastatic lesions in the brain and adrenal glands. The patient underwent a biopsy of the lesion in the right chest wall. The pathological and immunohistochemical findings indicated a high possibility of male breast cancer. However, the clinical features did not support this diagnosis. Therefore, a CT-guided percutaneous lung biopsy was performed, and the pathological examination finally indicated HG-FLAC. Conclusions: We presented a complex yet interesting case in which HG-FLAC was misdiagnosed as male breast cancer. Our interesting case may stimulate discussions about the methods to manage patients with HG-FLAC.

Application of integrated problem-based learning combined with lecture-based classroom teaching in undergraduate medical education: An effective teaching model in a Medical School in China.

The problem-based learning (PBL) is increasingly used in undergraduate education. However, the application of integrated PBL to medical undergraduate education has not been well assessed. An observational study was designed to compare integrated PBL combined with lecture-based classroom (LBC) with traditional LBC teaching in 2 semesters of a Medical School in China. This study was conducted from March 2021 to July 2022. A total of 118 undergraduates majoring in clinical medicine were randomly allocated in 2 groups, 1 group receiving the integrated PBL + LBC teaching (experimental group, n = 60) and another group receiving LBC teaching (control group, n = 58). The experimental group attended the integrated PBL courses for the basic and clinical medicine conducted in the 6th and 8th semesters, respectively, as well as taking the LBC courses. The experimental group was required to preview the course materials before class, make presentations in class and take online feedback questionnaires after class, while the control group was required to preview the textbooks and listen to the traditional LBC courses. The students' scores of these 2 groups were compared, and feedback questionnaires were performed to evaluate the effectiveness of the experimental group over the control group. Results showed that the experimental group scored significantly higher than the control group in Clinical Skills (95% confidence interval [CI] 4.19-5.89), Internal Medicine I (95% CI: 1.85-9.93), Internal Medicine II (95% CI: 8.07-15.90), Introduction to Surgery (95% CI: 5.08-10.25), Surgery (General Surgery) (95% CI: 7.82-12.72), Surgery (Specialty) (95% CI: 6.47-9.97), and Clinical Medical Level Test (95% CI: 1.60-5.15) (all P < .01). In the feedback questionnaires of integrated PBL, up to 80% and 90% of students were satisfied with the teaching methods and lecturers, respectively. More than 80% of students agreed that the integrated PBL improved their abilities to learn independently, understand knowledge, and to raise, analyze and solve problems. In terms of stress in and out of class, a small number of students, <36.7%, felt stressed. The integrated PBL combined with LBC is an effective teaching approach, which may provide new ideas for teaching research and reform on undergraduate medical education in clinical medicine specialty and other medical majors.

Expression of p53 as a biomarker in determining response to apatinib for advanced gastric cancer.

Background: Apatinib has shown outstanding value in the treatment of advanced gastric cancer (AGC). However, no biomarkers are available to select AGC patients who will benefit from apatinib. The aim of the present study was to investigate the association between p53 and Ki67 expression of and the outcome in AGC patients treated with apatinib. Methods: From December 2015 to December 2020, 92 AGC patients were enrolled and was retrospectively evaluated. They were given apatinib at a daily dose of 500 or 250 mg every 4 weeks to monitor clinical efficacy and adverse events (AEs). Kaplan-Meier method was used for survival analysis. Expression of p53 and Ki67 was detected by immunohistochemistry (IHC) and correlated with survival. Results: Among 92 evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 17.4% and 79.3%, respectively, and none of them achieved a CR, 16 achieved a PR (17.4%) (95% CI 9.8%-26.1%). Stable disease (SD) was observed in 57.6% of patients (95% CI 49.2%-69.9%) and PD in 21.7% of patients (95% CI 13.6%-31.3%). The median progression free survival (mPFS) was 122.7 ± 8.2 days, and the median overall survival (mOS) was 203.4 ± 11.9 days. P53 expression was observed in 35 patients (38.0%) and high expression of Ki67 was detected in 34 patients (37.0%). There was a statistically significant inverse relationship between p53 and Ki67 expression (P=0.014). Moreover, p53 was significantly correlated with the OS (P=0.018), but Ki67 had no significant influence on OS. Conclusions: Apatinib showed promising efficiency and was well tolerated as a second-line treatment for AGC patients. AGC patients with p53-negative were likely to benefit from apatinib treatment; however, the expression of Ki67 proteins has no significant impact on the outcome of AGC patients.

Recent Advances on Single-Atom Catalysts for Photocatalytic CO2 Reduction.

The present energy crisis and environmental challenges may be efficiently resolved by converting carbon dioxide (CO2 ) into various useful carbon products. The development of more effective catalysts has been the main focus of current research on photocatalytic CO2 reduction. Due to their high atomic efficiency and superior catalytic activity, single-atom catalysts (SACs) have attracted considerable interest in catalytic CO2 conversion. This review discusses the current research developments, obstacles, and potential of SACs for photocatalytic CO2 reduction. And further, discusses the principle of photocatalytic carbon dioxide reduction. This work has compared and analyzed the effects of support materials and active site types in SACs on photocatalytic CO2 reduction performance. This work believes that by sharing these developments, some inspiration for the rational design and development of stable and effective photocatalytic CO2 reduction catalysts based on SACs can be provided.

Mechanism by which oleracein E alleviates TNBS-induced ulcerative colitis.

OBJECTIVE: This study aimed to investigate the effect of oleracein E (OE) in improving 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC). METHODS: Lipopolysaccharide (LPS) was used to induce a UC cell model, and TNBS was used to induce a UC rat model. ELISA was performed to assess the levels of inflammatory factors (IL-1ß, TNF-α, and IL-6). Moreover, the activities of catalase (CAT), myeloperoxidase (MPO), and malonaldehyde (MDA) were detected by kits. Western blotting was performed to assess related proteins of the Nrf2/HO-1 signaling pathway, tight junction protein (ZO-1, Occludin, and claudin-2) expression levels, and apoptosis-related proteins (Bcl2, Bax, and cleaved caspase 3). Flow cytometry was used to analyze ROS levels. The morphology of colon tissues and the apoptosis of cells were detected by HE and TUNEL staining, respectively. RESULTS: OE significantly increased the activity of CAT and decreased the activity of MPO in LPS-induced Caco-2 cells and TNBS-induced UC rats. However, the levels of IL-1ß, IL-6, and TNF-α were markedly reduced both in vivo and in vitro. In addition, OE significantly increased the levels of Nrf2/HO-1 signaling pathway-related proteins and tight junction proteins and inhibited cell apoptosis. HE staining showed that OE significantly decreased the severity of acute TNBS-induced colitis in rats. CONCLUSION: OE may exert a regulatory effect on ameliorating intestinal barrier injury and reducing inflammation and oxidative stress levels by activating the Nrf2/HO-1 pathway.

Transcriptomic analysis reveals the potential biological mechanism of AIS and lung adenocarcinoma.

Introduction: Acute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD. Methods: Transcriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines. Results: We identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A, and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling. Discussion: Our findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.

The role and molecular mechanism of metabolic reprogramming of colorectal cancer by UBR5 through PYK2 regulation of OXPHOS expression study.

Colorectal carcinoma (CRC) is the third most malignant tumor in the world, but the key mechanisms of CRC progression have not been confirmed. UBR5 and PYK2 expression levels were detected by RT-qPCR. The levels of UBR5, PYK2, and mitochondrial oxidative phosphorylation (OXPHOS) complexes were detected by western blot analysis. Flow cytometry was used to detect ROS activity. The CCK-8 assay was used to assess cell proliferation and viability. The interaction between UBR5 and PYK2 was detected by immunoprecipitation. A clone formation assay was used to determine the cell clone formation rate. The ATP level and lactate production of each group of cells were detected by the kit. EdU staining was performed for cell proliferation.Transwell assay was performed for cell migration ability. For the CRC nude mouse model, we also observed and recorded the volume and mass of tumor-forming tumors. The expression of UBR5 and PYK2 was elevated in both CRC and human colonic mucosal epithelial cell lines, and knockdown of UBR5 had inhibitory effects on cancer cell proliferation and cloning and other behaviors in the CRC process by knockdown of UBR5 to downregulate the expression of PYK2, thus inhibiting the OXPHOS process in CRC; rotenone (OXPHOS inhibitor) treatment enhanced all these inhibitory effects. Knockdown of UBR5 can reduce the expression level of PYK2, thus downregulating the OXPHOS process in CRC cell lines and inhibiting the CRC metabolic reprogramming process.

Genetic analysis of periventricular nodular heterotopia 7 caused by a novel NEDD4L missense mutation: Case and literature summary.

BACKGROUND: Neurodevelopmental disorders associated with periventricular nodular heterotopia (PVNH) are characterized by phenotypic and genetic heterogeneity. NEDD4L mutation can lead to PVNH7. However, at present, only eight NEDD4L pathogenic variants have been identified across 15 cases of PVNH7 worldwide. Given this dearth of evidence, the precise correlations between genetic pathogenesis and phenotypes remain to be determined. METHODS: This report discusses the case of a 19-month-old male child with cleft palate, seizures, psychomotor retardation, and hypotonia, for whom we verified the genetic etiology using Trio-whole-exome and Sanger sequencing to analyze the potential pathogenicity of the mutant protein structure. Mutant plasmids were constructed for in vitro analyses. After transfection into human 293 T cells, the mutant transcription process was analyzed using real-time PCR (RT-PCR), and levels of mutant protein expression were examined using western blotting (WB) and immunofluorescence (IF) experiments. RESULTS: Genetic analyses revealed a novel missense mutation Gln900Arg, located in the homologous to E6-APC terminal (HECT) domain of NEDD4L and that the parents were wild-type, suggestive of a de novo mutation. The variant was predicted to be pathogenic by bioinformatics software, which also suggested alterations in the structural stability of the mutant protein. RT-PCR results indicated that the mutation did not affect mRNA expression, whereas WB and IF results indicated that the level of mutant protein was significantly reduced by 41.07%. CONCLUSION: Functional experiments demonstrated that Gln900Arg probably did not lead to transcriptional abnormalities in this patient, instead leading to increased ubiquitination activity owing to the constitutive activation of the HECT domain, thereby promoting protein degradation. Extensive clinical reports should be generated for patients presenting with PVNH and/or polymicrogyria, developmental delay, syndactyly, and hypotonia to increase the pool of evidence related to NEDD4L.

Study on Synthesizing Isobornyl Acetate/Isoborneol from Camphene Using α-Hydroxyl Carboxylic Acid Composite Catalyst.

This study examined the preparation of isobornyl acetate/isoborneol from camphene using an α-hydroxyl carboxylic acid (HCA) composite catalyst. Through the study of the influencing factors, it was found that HCA and boric acid exhibited significant synergistic catalysis. Under optimal conditions, when tartaric acid-boric acid was used as the catalyst, the conversion of camphene and the gas chromatography (GC) content and selectivity of isobornyl acetate were 92.9%, 88.5%, and 95.3%, respectively. With the increase in the ratio of water to acetic acid, the GC content and selectivity of isobornol in the product increased, but the conversion of camphene decreased. The yield of isobornol was increased by adding ethyl acetate or titanium sulfate/zirconium sulfate to form a ternary composite catalyst. When a ternary complex of titanium sulfate, tartaric acid, and boric acid was used as the catalyst, the GC content of isobornol in the product reached 55.6%. Under solvent-free conditions, mandelic acid-boric acid could catalyze the hydration reaction of camphene, the GC content of isoborneol in the product reached 26.1%, and the selectivity of isoborneol was 55.9%. The HCA-boric acid composite catalyst can use aqueous acetic acid as a raw material, which is also beneficial for the reuse of the catalyst.

High level of tumor marker CA19-9 returned to normal after cholecystectomy in calculous cholecystitis patients.

BACKGROUND: High serum CA19-9 is usually caused by pancreaticobiliary malignancies, but it has also been found in a tiny minority of calculous cholecystitis patients. AIMS: To clarify the relationship between calculous cholecystitis and serum CA19-9. METHODS: Clinical data of calculous cholecystitis patients with high serum CA19-9 (high group, n = 20) and normal serum CA19-9 (normal group, n = 40) who underwent cholecystectomy were analyzed. Serum CA19-9 of high group were followed-up and gallbladder specimens were analyzed by immunohistochemistry. RESULTS: Serum CA19-9 in the high group ranged from 105 to 1635 U/ml, of which 30% exceeded 1000 U/ml. Follow-up results showed that 20 patient's serum CA19-9 returned to normal after cholecystectomy, including 4 closely followed-up patients whose serum CA19-9 recovered within one month. Immunohistochemical results revealed that CA19-9 was mildly positive only in mucosal epithelial cells in the normal group, but positive in mucosal epithelial cells, vascular endothelial cells, and intercellular substances in the high group, accounting for high serum CA19-9. CONCLUSION: Serum CA19-9 is proved to be associated with calculous cholecystitis for the first time, so that clinicians should consider calculous cholecystitis associated CA19-9 elevation in the clinic practice besides other CA19-9 related diseases.