Mechanically reinforced hydrogel vehicle delivering angiogenic factor for beta cell therapy.

Type 1 diabetes mellitus (T1DM) is a chronic disease affecting millions worldwide. Insulin therapy is currently the golden standard for treating T1DM; however, it does not restore the normal glycaemic balance entirely, which increases the risk of secondary complications. Beta-cell therapy may be a possible way of curing T1DM and has already shown promising results in the clinic. However, low retention rates, poor cell survival, and limited therapeutic potential are ongoing challenges, thus increasing the need for better cell encapsulation devices. This study aimed to develop a mechanically reinforced vascular endothelial growth factor (VEGF)-delivering encapsulation device suitable for beta cell encapsulation and transplantation. Poly(l-lactide-co-ε-caprolactone) (PLCL)/gelatin methacryloyl (GelMA)/alginate coaxial nanofibres were produced using electrospinning and embedded in an alginate hydrogel. The encapsulation device was physically and biologically characterised and was found to be suitable for INS-1E beta cell encapsulation, vascularization, and transplantation in terms of its biocompatibility, porosity, swelling ratio and mechanical properties. Lastly, VEGF was incorporated into the hydrogel and the release kinetics and functional studies revealed a sustained release of bioactive VEGF for at least 14 days, making the modified alginate system a promising candidate for improving the beta cell survival after transplantation.

PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.

BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.

Emerging Strategies for Beta Cell Encapsulation for Type 1 Diabetes Therapy.

Diabetes is a prevalent chronic disease affecting millions of people globally. To address this health challenge, advanced beta cell therapy using biomaterials-based macroscale, microscale, and nanoscale encapsulation devices must tackle various obstacles. First, overcoming foreign body responses is a major focus of research. Strategies such as immunomodulatory materials and physical immunoshielding are investigated to reduce the immune response and improve the longevity of the encapsulated cells. Furthermore, oxygenating strategies, such as the use of oxygen-releasing biomaterials, are developed to improve oxygen diffusion and promote cell survival. Finally, yet importantly, promoting vascularization through the use of angiogenic growth factors and the incorporation of pre-vascularized materials are also explored to enhance nutrient and oxygen supply to the encapsulated cells. This review seeks to specifically highlight the emerging research strategies developed to overcome these challenges using micro and nanoscale biomaterial encapsulation devices. Continuously improving and refining these strategies make an advance toward realizing the improved therapeutic potential of the encapsulated beta cells.

Nobiletin targets SREBP1/ACLY to induce autophagy-dependent cell death of gastric cancer cells through PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Autophagy could sense metabolic conditions and safeguard cells against nutrient deprivation, ultimately supporting the survival of cancer cells. Nobiletin (NOB) is a kind of bioactive component of the traditional Chinese medicine Citri Reticulatae Pericarpium and has been proven to induce GC cell death by reducing de novo fatty acid synthesis in our previous study. Nevertheless, the precise mechanisms by which NOB induces cell death in GC cells still need further elucidation. OBJECTIVES: To examine the mechanism by which NOB inhibits gastric cancer progression through the regulation of autophagy under the condition of lipid metabolism inhibition. METHODS/ STUDY DESIGN: Proliferation was detected by the CCK-8 assay. RNA sequencing (RNA-seq) was used to examine signaling pathway changes. Electron microscopy and mRFP-GFP-LC3 lentiviral transfection were performed to observe autophagy in vitro. Western blot, plasmid transfection, immunofluorescence staining, and CUT & Tag-qPCR techniques were utilized to explore the mechanisms by which NOB affects GC cells. Molecular docking and molecular dynamics simulations were conducted to predict the binding mode of NOB and SREBP1. CETSA was adopted to verify the predicted of binding model. A patient-derived xenograft (PDX) model was employed to verify the therapeutic efficacy of NOB in vivo. RESULTS: We conducted functional studies and discovered that NOB inhibited the protective effect of autophagy via the PI3K/Akt/mTOR axis in GC cells. Based on previous research, we found that the overexpression of ACLY abrogated the NOB-induced autophagy-dependent cell death. In silico analysis predicted the formation of a stable complex between NOB and SREBP1. In vitro assays confirmed that NOB treatment increased the thermal stability of SREBP1 at the same temperature conditions. Moreover, CUT&TAG-qPCR analysis revealed that NOB could inhibit SREBP1 binding to the ACLY promoter. In the PDX model, NOB suppressed tumor growth, causing SREBP1 nuclear translocation inhibition, PI3K/Akt/mTOR inactivation, and autophagy-dependent cell death. CONCLUSION: NOB demonstrated the ability to directly bind to SREBP1, inhibiting its nuclear translocation and binding to the ACLY promoter, thereby inducing autophagy-dependent cell death via PI3K/Akt/mTOR pathway.

Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection.

Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities. Methods: The AlCl3 colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti - oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18 column (2.0 mm × 150 mm, 5 µm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase (PDB ID: 2CDU) by molecular docking. Results: Combined with the results of activity screening in vitro, the anti - oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatography-mass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile. Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.

Application of Multicolor Fluorescent Carbon Dots Based on Tea Polyphenols in a White Light-Emitting Diode and Room-Temperature Phosphorescence.

Carbon dots (CDs) are new carbon nanomaterials, among which those prepared from biomass are popular due to their excellent optical properties and environmental friendliness. As representative natural phenolic compounds, tea polyphenols are ideal precursors with fluorescent aromatic rings and phenolic hydroxyl structures. Usually, polyphenolic precursors can only be used to produce blue or green fluorescent CDs, and fluorescence in long wavelength domains, such as orange or red, cannot be achieved. Herein, the high reactivity of the phenolic hydroxyl groups in tea polyphenols with o-phthalaldehyde was exploited to modulate the pH during the carbonation process, which led to redshifts of the fluorescence wavelengths. Different pH values during the reaction caused the precursors to take different reaction paths and form fluorescent groups exhibiting different conjugated structures, resulting in carbon dots providing different fluorescent colors. Finally, by utilizing the in situ hydrolysis of ethyl orthosilicate, the tea polyphenol-based carbon dots were embedded into a silica matrix, inducing phosphorescence of the carbon dots. This study provides a new approach for green preparation and application of natural polyphenolic CDs.

Aminated graphene quantum dots/CdS nanobelts for enhanced photocatalytic degradation of RhB dye under visible light.

CdS nanoparticles have wide applications as photocatalysts for degradation of organic pollutants, but due to their limited turnover number and off-pathway charge recombination processes, their degradation efficiency is low. Herein, aminated graphene quantum dots/CdS (GQDs/CdS) nanobelts were successfully fabricated by solvothermal and hydrothermal processes. The prepared GQDs/CdS were characterized by physical methods to investigate their structure, morphology, optical properties, specific surface area, element composition, and chemical state. GQDs/CdS materials promoted efficient charge separation, and showed high efficiency in the photocatalytic degradation of the organic dye Rhodamine B (RhB) under visible light. The degradation efficiency of RhB samples over 0.05 g of catalysts reached 97.40% after 150 min, a much higher efficiency in comparison to pure CdS. Electron paramagnetic resonance (EPR) spectroscopy provided direct evidence for ˙OH and ˙O2- as the reactive oxidative species using DMPO as a spin trap. Consistent with the experimental results, a possible mechanism of RhB photocatalytic degradation by GQDs/CdS under visible light was proposed. This work may provide environmentally friendly photocatalysts for degrading organic dyes and purifying water.

The emerging role of glycolysis and immune evasion in gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a "predominantly glycolytic" metabolic pattern to promote its survival and metastasis, also known as "the Warburg effect", which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC.

Coexistence of large-area topological pseudospin and valley states in a tri-band heterostructure system.

The rapid development of topological photonics has significantly revolutionized our comprehension of electromagnetic wave manipulation in recent decades. Recent research exploiting large-area topological states inserts an additional gapless PC structure between topologically trivial and nontrivial PCs, effectively introducing the mode width degree of freedom. Nevertheless, these heterostructures mainly support only single-type waveguide states operating within a single frequency band. To address these limitations, we propose a novel, to the best of our knowledge, tri-band three-layer heterostructure system, supporting both large-area pseudospin- and valley-locked states. The system showcases tunable mode widths with different operational bandwidths. Moreover, the heterostructures exhibit inherent topological characteristics and reflection-free interfacing, which are verified in the well-designed Z-shaped channels. The proposed heterostructure system can be used to design multi-band multi-functional high-flexibility topological devices, providing great advantages for enlarging the on-chip integrated communication systems.

Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages. METHODS: Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6-/-) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells. RESULTS: We observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC. CONCLUSION: In summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.

Performance and microbial metabolic mechanism of imidacloprid removal in a microbial electrolysis cell-integrated adsorption biological coupling system.

Coke used as a filler to treat imidacloprid (IMI) wastewater by both adsorption biological coupling and microbial electrolysis cells (MEC)-adsorption biological coupling technologies, the removal efficiencies on pollutions in wastewater containing IMI were investigated, and the key functional genes related to IMI degradation pathways were also revealed. Results showed that the removal rates of COD, ammonia nitrogen, TP, and IMI under the adsorption biological coupling treatment and MEC-adsorption biological coupling treatment were 94.61-95.54%, 93.37-95.79%, 73.69-83.80%, and 100%, respectively. MEC increased the relative abundance of Proteobacteria by 9.01% and transformed the dominant bacteria from Lysobacter and Reyranella to Brevundimonas and Aquincola. Moreover, MEC up-regulated the abundance of the coding genes PK (9.30%), narG (2.26%), pstS (3.63%), and phnD (1.32%), and converted the IMI degradation products to smaller molecular weight C6H8N2 and C6H6ClNO. This study provided an important reference information for efficient treatment of IMI wastewater using the MEC-adsorption biological coupling technology.

Nobiletin inhibits de novo FA synthesis to alleviate gastric cancer progression by regulating endoplasmic reticulum stress.

BACKGROUND: Gastric cancer (GC) is a common malignant tumor with limited treatment options. The natural flavonoid nobiletin (NOB) is a beneficial antioxidant that possesses anticancer activity. However, the mechanisms by which NOB inhibits GC progression remain unclear. METHODS: A CCK-8 assay was performed to determine cytotoxicity. Cell cycle and apoptosis analyses were performed by flow cytometry. RNA-seq was performed to detect differential gene expression after NOB treatment. RT‒qPCR, Western blot and immunofluorescence staining were used to examine the underlying mechanisms of NOB in GC. Xenograft tumor models were constructed to verify the effect of NOB and its specific biological mechanism in GC. RESULTS: NOB inhibited cell proliferation, caused cell cycle arrest and induced apoptosis in GC cells. KEGG classification identified that the inhibitory effect of NOB on GC cells mainly involved the lipid metabolism pathway. We further showed that NOB reduced de novo fatty acid (FA) synthesis, as evidenced by the decreased levels of neutral lipids and the expression levels of ACLY, ACACA and FASN, and ACLY abrogated the effect of NOB on lipid deposits in GC cells. In addition, we also found that NOB triggered endoplasmic reticulum (ER) stress by activating the IRE-1α/GRP78/CHOP axis, but overexpression of ACLY reversed ER stress. Mechanistically, inhibiting ACLY expression with NOB significantly reduced neutral lipid accumulation, thereby inducing apoptosis by activating IRE-1α-mediated ER stress and inhibiting GC cell progression. Finally, in vivo results also demonstrated that NOB inhibited tumor growth by decreasing de novo FA synthesis. CONCLUSION: NOB could inhibit the expression of ACLY to activate IRE-1α-induced ER stress, which ultimately led to GC cell apoptosis. Our results provide novel insight into the use of de novo FA synthesis for GC treatment and are the first to reveal that NOB inhibits GC progression by ACLY-dependent ER stress.

Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS: GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

Jianpi Yangzheng decoction suppresses gastric cancer progression via modulating the miR-448/CLDN18.2 mediated YAP/TAZ signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Developing complementary and effective drugs with less toxicity is urgent for gastric cancer (GC) therapy. Jianpi Yangzheng Decoction (JPYZ) is a curative medical plants formula against GC in clinic while its molecular mechanism remains to be further elucidated. AIM OF THE STUDY: To evaluate the in vitro and in vivo anticancer efficacy of JPYZ against GC and its potential mechanisms. MATERIALS AND METHODS: The effect of JPYZ on regulating the candidate targets were screened and examined by RNA-Seq, qRT-PCR, luciferase reporter assay, and immunoblotting. Rescue experiment was conducted to authenticate the regulation of JPYZ on the target gene. Molecular interaction, intracellular localization and function of target genes were elucidated via Co-IP and cytoplasmic-nuclear fractionation. The impact of JPYZ on the abundance of target gene in clinical specimens of GC patients was evaluated by IHC. RESULTS: JPYZ treatment suppressed the proliferation and metastasis of GC cells. RNA seq revealed JPYZ significantly downregulated miR-448. A reporter plasmid containing CLDN18 3'-UTR WT exhibited significant decrease in luciferase activity when co-transfected with miR-448 mimic in GC cells. CLDN18.2 deficiency promoted the proliferation and metastasis of GC cells in vitro, as well as intensified the growth of GC xenograft in mice. JPYZ reduced the proliferation and metastasis of GC cells with CLDN18.2 abrogation. Mechanically, suppressed activities of transcriptional coactivator YAP/TAZ and its downstream targets were observed in GC cells with CLDN18.2 overexpression and those under JPYZ treatment, leading to cytoplasmic retention of phosphorylated YAP at site Ser-127. High abundance of CLDN18.2 was detected in more GC patients who received chemotherapy combined with JPYZ. CONCLUSION: JPYZ has an inhibitory effect on GC growth and metastasis partly by elevating CLDN18.2 abundance in GC cells, indicating more patients may benefit from combination therapy of JPYZ and the upcoming CLDN18.2 target agents.

Endometriosis in an ectopic kidney: a rare case report and literature review.

BACKGROUND: Endometriosis mainly occurs in female pelvic organs. Endometriosis in the kidney is extremely rare. CASE PRESENTATION: We herein describe a case of a 19-year-old girl with occasional mild abdominal pain associated with an ectopic left kidney. SPECT-CT showed no abnormal radioactive distribution in the left pelvis, suggesting loss of function of the ectopic kidney. Laparoscopic left ectopic kidney resection was subsequently performed. Histopathology revealed endometriosis of the ectopic left kidney. CONCLUSIONS: In female patients with clinical manifestations of abdominal pain and gross hematuria, the possibility of renal endometriosis should be considered.

Effects of perfluoroalkyl substances on the operational efficiency, microbial communities, and key metabolic pathways of constructed rapid infiltration system with coke as filler layer.

Influences of perfluoroalkyl substances on the performance and microbial metabolic pathways of constructed rapid infiltration systems are not fully understood. In this study, wastewater containing different concentrations of perfluorooctanoic acid (PFOA)/perfluorobutyric acid (PFBA) was treated in constructed rapid infiltration systems with coke as filler. The addition of 5 and 10 mg/L PFOA inhibited the removal of chemical oxygen demand (COD) (80.42%, 89.27%), ammonia nitrogen (31.32%, 41.14%), and total phosphorus (TP) (43.30%, 39.34%). Meanwhile, 10 mg/L PFBA inhibited TP removal of the systems. Based on X-ray photoelectron spectroscopy, the percentages of F- within the PFOA and PFBA groups were 12.91% and 48.46%, respectively. PFOA transformed Proteobacteria (71.79%) into the dominant phyla of the systems, whereas PFBA enriched Actinobacteria (72.51%). The PFBA up-regulated the coding gene of 6-phosphofructokinase by 14.44%, whereas PFOA down-regulated it by 4.76%. These findings provide insights into the toxicity of perfluoroalkyl substances on constructed rapid infiltration systems.

Formation and Band Gap Tuning Mechanism of Multicolor Emissive Carbon Dots from m-Hydroxybenzaldehyde.

Reported in 2004, carbon dots (CDs) have been widely used in various fields due to their excellent optical properties. However, the mechanism of their fluorescence modulation is still a controversial issue, which also seriously affects the further development of carbon dots. In this paper, m-hydroxybenzaldehyde is used as a raw material to obtain multicolor luminescent CDs by pyrolysis under different reaction conditions, thereby revealing the forbidden band tuning and formation mechanism of CDs. Different acid-base conditions lead to different reaction paths of the precursors, forming molecular fluorophores with different conjugated structures, which aggregate to eventually form CDs and further enhance the photoluminescence of the system by inhibiting the movement of the fluorescent centers.

Fe(III) enhances Cr(VI) bioreduction in a MFC-granular sludge coupling system: Experimental evidence and metagenomics analysis.

The influence of Fe(III) on the bioreduction efficiency of Cr(VI) in a microbial fuel cell (MFC)-granular sludge coupling system using dissolved methane as an electron donor and carbon source was explored, and the mechanism of Fe(III) mediating enhancement in the bioreduction process of Cr(VI) in the coupling system was also investigated. Results showed that the presence of Fe(III) enhanced the ability of the coupling system to reduce Cr(VI). The average removal efficiencies of Cr(VI) in the anaerobic zone in response to 0, 5, and 20 mg/L of Fe(III) were 16.53±2.12%, 24.17±2.10%, and 46.33±4.41%, respectively. Fe(III) improved the reducing ability and output power of the system. In addition, Fe(III) enhanced the electron transport systems activity of the sludge, the polysaccharide and protein content in the anaerobic sludge. Meanwhile, X-ray photoelectron spectrometer (XPS) spectra demonstrated that Cr(VI) was reduced to Cr(III), while Fe2p participated in reducing Cr(VI) in the form of Fe(III) and Fe(II). Proteobacteria, Chloroflexi, and Bacteroidetes were the dominant phylum in the Fe(III)-enhanced MFC-granular sludge coupling system, accounting for 49.7%-81.83% of the microbial community. The relative abundance of Syntrophobacter and Geobacter increased after adding Fe(III), indicating that Fe(III) contributed to the microbial mediated anaerobic oxidation of methane (AOM) and bioreduction of Cr(VI). The genes mcr, hdr, and mtr were highly expressed in the coupling system after the Fe(III) concentration increased. Meanwhile, the relative abundances of coo and aacs genes were up-regulated by 0.014% and 0.075%, respectively. Overall, these findings deepen understanding of the mechanism of the Cr(VI) bioreduction in the MFC-granular sludge coupling system driven by methane under the influence of Fe(III).

HDAC3 Controls Liver Homeostasis More by Facilitating Deoxyribonucleic Acid Damage Repair than by Regulating Transcription in Hepatocytes.

By controlling DNA damage repair and regulating gene transcription, the critical epigenetic regulator histone deacetylase 3 (HDAC3) plays pivotal roles in liver cancer and liver regeneration; however, the role of HDAC3 in liver homeostasis has not been fully elucidated. In this study, we found that HDAC3-deficient livers developed a defective morphology and metabolism with an increasing degree of DNA damage in the hepatocytes along the portal-central axis of the lobule. Most strikingly, in the Alb-CreERT:Hdac3-/- mice, it was demonstrated that HDAC3 ablation did not impair liver homeostasis in terms of histologic characteristics, function, proliferation, or gene profiles prior to the profound accumulation of DNA damage. Next, we identified that the hepatocytes in the portal area, which carried less DNA damage than those in the central area, repopulated the hepatic lobule by active regeneration and movement toward the center. As a result, the liver became more viable after each surgery. Furthermore, in vivo tracing of keratin-19-expressing hepatic progenitor cells, which lacked HDAC3, showed that the hepatic progenitor cells gave rise to newly generated periportal hepatocytes. In hepatocellular carcinoma, HDAC3 deficiency impaired DNA damage response and enhanced radiotherapy sensitivity in vitro and in vivo. Taken together, we demonstrated that HDAC3 deficiency interferes with liver homeostasis, which is more dependent on the accumulation of DNA damage in hepatocytes than on transcriptional dysregulation. Our findings support the hypothesis that selective HDAC3 inhibition has the potential to augment the effect of chemoradiotherapy aimed at inducing DNA damage in cancer therapy.