Complications After Prepectoral Versus Subpectoral Breast Reconstruction in Patients Receiving Postmastectomy Radiation Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Outcomes of immediate breast reconstructions can be influenced by postoperative radiotherapy. However, there is no clarity on the use of prepectoral or subpectoral breast reconstruction in the setting of postmastectomy radiation therapy (PMRT). We reviewed evidence on the complication rates of prepectoral and subpectoral breast reconstruction in women undergoing PMRT. METHODS: PubMed, Web of Science, and Embase databases were scanned for studies comparing complication rates of prepectoral and subpectoral breast reconstruction with PMRT. All complications were pooled in a random-effect meta-analysis to obtain odds ratio (OR). RESULTS: Eight observational studies were included. Meta-analysis showed no difference in the risk of infections (OR: 1.22 95% CI 0.79, 1.88 I2=0%), implant loss (OR: 0.86 95% CI 0.50, 1.50 I2=14%), seroma (OR: 1.01 95% CI 0.43, 2.34 I2=50%), hematoma (OR: 0.44 95% CI 0.12, 1.71 I2=0%), wound dehiscence (OR: 0.95 95% CI 0.42, 2.17 I2=0%), and skin necrosis (OR: 0.61 95% CI 0.21, 1.75 I2=36%), contracture (OR: 0.46 95% CI 0.15, 1.48 I2=54%) and the need for revision surgeries (OR: 0.85 95% CI 0.45, 1.60 I2=15%) between the prepectoral and subpectoral groups. CONCLUSIONS: Data from observational studies indicates that in appropriately selected patients there may not be any difference in the risk of early complications with prepectoral or subpectoral breast reconstruction with PMRT. Current evidence is limited by the small number of studies, short follow-up and selection bias. There is a need for randomized controlled trials comparing the two approaches to obtain robust evidence on long-term outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical Results of Asymmetric Blepharoplasty Plastic Repair.

OBJECTIVE: To investigate plastic surgery repair's effects and adverse reactions in the clinical therapy of asymmetric double eyelids. METHODS: All 126 sufferers who came to the hospital for asymmetric double eyelid plastic repair from January 2022 to October 2022 were selected as the research objects, and they were divided into a control group and an observation group using the random number method, with 63 cases in each group, in which sufferers in the control group underwent full incision blepharoplasty and sufferers in the observation group underwent small incision liposuction with submerged sutures. The general data, treatment results, treatment satisfaction, related surgical indicators, and frequency of adverse reactions of the 2 groups of sufferers with asymmetric double eyelid plastic repair were compared. RESULTS: It had no statistically obvious distinction between the control group and the observation group of sufferers in terms of general data such as sex, age, weight, and height (P>0.05); the total therapy efficiency of the sufferers in the observation group (95.24%) was greater than the control group (74.60%), with P value <0.05; the total treatment satisfaction of the patients in the observation group (96.83%) was significantly higher than that in the control group (76.19%), with P value <0.05; compared with the control group, patients in the observation group had shorter operative time and healing time and less intraoperative bleeding, with P value <0.05; the total frequency of adverse reactions of sufferers in the observation group (4.76%) was less than the control group (17.46%), with P value <0.05. CONCLUSION: Small incision liposuction with submerged sutures for plastic repair has significant efficacy, relatively high patient satisfaction, and low incidence of adverse reactions, in line with patient esthetic review, which has a broad clinical application prospect.

Construction of Immune-Related Diagnostic Model for Latent Tuberculosis Infection and Active Tuberculosis.

Background: Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging. Methods: Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set. Results: Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI. Conclusion: Our study may provide implications for the diagnosis and drug development of M. tb infections.

Chronic exposure to low concentrations of microplastics causing gut tissue damage but non-significant changes in the microbiota of marine medaka larvae (Oryzias melastigma).

Microplastics (MPs) have become a popular research topic due to their potential ramifications on aquatic organisms. To evaluate the ecotoxicological impacts of chronic exposure to different microplastics on marine medaka larvae, we exposed medaka larvae to 200 µg/L of polyethylene (PE-200) and polylactic acid (PLA-200) microplastics for 60 days, respectively. The results indicated that both exposures had no significant effect on fish length/weight and did not result in fish mortality. Notably, the structure of intestinal microbiota was not disrupted either. However, microscopy observations of intestinal tissue suggested that exposure to MPs resulted in inflammation of the intestinal tract of fish and significant atrophy and shedding of small intestinal villus. Linear discriminant analysis Effect Size (LEfSe) showed that intestinal enrichment of Streptomyces occurred in marine medaka larvae in both MPs treatments, while the PE-200 treatment exhibited a significant enrichment. In addition, the PICRUSt2 prediction indicated significant upregulation of the Novobiocin biosynthesis function in gut microbiota in the PE-200 treatment. Overall, multi-level assessment is necessary to determine the risk of exposure of aquatic organisms to MPs.

SHMT2 promotes papillary thyroid cancer metastasis through epigenetic activation of AKT signaling.

Cancer cells alter their metabolism and epigenetics to support cancer progression. However, very few modulators connecting metabolism and epigenetics have been uncovered. Here, we reveal that serine hydroxymethyltransferase-2 (SHMT2) generates S-adenosylmethionine (SAM) to epigenetically repress phosphatase and tensin homolog (PTEN), leading to papillary thyroid cancer (PTC) metastasis depending on activation of AKT signaling. SHMT2 is elevated in PTC, and is associated with poor prognosis. Overexpressed SHMT2 promotes PTC metastasis both in vitro and in vivo. Proteomic enrichment analysis shows that AKT signaling is activated, and is positively associated with SHMT2 in PTC specimens. Blocking AKT activation eliminates the effects of SHMT2 on promoting PTC metastasis. Furthermore, SHMT2 expression is negatively associated with PTEN, a negative AKT regulator, in PTC specimens. Mechanistically, SHMT2 catalyzes serine metabolism and produces activated one-carbon units that can generate SAM for the methylation of CpG islands in PTEN promoter for PTEN suppression and following AKT activation. Importantly, interference with PTEN expression affects SHMT2 function by promoting AKT signaling activation and PTC metastasis. Collectively, our research demonstrates that SHMT2 connects metabolic reprogramming and epigenetics, contributing to the poor progression of PTC.

Distribution characteristics of antibiotic resistance genes and microbial diversity in the inshore aquaculture area of Wenchang, Hainan, China.

The rapid development of marine aquaculture has led to the increased use and release of antibiotics into the marine environment, consequently contributing to the emergence of antibiotic resistance. Information on antibiotic resistance in nearshore marine aquaculture areas remains limited, and research on the microbial composition and potential hosts of antibiotic resistance genes (ARGs) in marine aquaculture areas is scarce. This study used SmartChip real-time fluorescent quantitative PCR and qPCR to quantitatively analyze 44 ARGs and 10 mobile genetic elements (MGEs) genes in 12 sampling points in the nearshore aquaculture area of Wenchang. High-throughput sequencing of 16S rRNA was used to study microbial diversity in the study area, to clarify the correlation between ARGs, MGEs, and microbial diversity, and to determine the possible sources and potential hosts of ARGs. The results showed that a total of 37 ARGs and 8 MGEs were detected in the study area. The detection rate of 9 ARGs (aac(6')-Ib(aka aacA4)-02, catA1, cmlA, cfr, sul1, sul2, sulA/folP-01, tetC, tetX) was 100 %. The absolute abundance of ARGs in the 12 sampling points ranged from 2.75 × 107 to 3.79 × 1010 copies·L-1, and the absolute abundance of MGEs was 1.30 × 105 to 2.54 × 107 copies·L-1, which was relatively high compared to other research areas. ARGs and MGEs were significantly correlated, indicating that MGEs play an important role as a mediator in the spread of ARGs. At the phylum level, Proteobacteria and Cyanobacteria were the dominant bacteria in the study area, with HIMB11 and unidentifiedChloroplast being the dominant levels, respectively. Network analysis of ARGs and microorganisms (genus level) revealed that Cognatishimia, Thalassobius, Aestuariicoccus, Thalassotalea, and Vibrio were significantly correlated with multiple ARGs and were the main potential hosts of ARGs in the nearshore waters of Wenchang.

ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.

Mitochondria dysfunction contributes to acute liver injuries, and mitochondrial regulators, such as PGC-1α and MCJ, affect liver regeneration. Therefore, identification of mitochondrial modulators may pave the way for developing therapeutic strategies. Here, ZHX2 is identified as a mitochondrial regulator during acute liver injury. ZHX2 both transcriptionally inhibits expression of several mitochondrial electron transport chain genes and decreases PGC-1α stability, leading to reduction of mitochondrial mass and OXPHOS. Loss of Zhx2 promotes liver recovery by increasing mitochondrial OXPHOS in mice with partial hepatectomy or CCl4-induced liver injury, and inhibition of PGC-1α or electron transport chain abolishes these effects. Notably, ZHX2 expression is higher in liver tissues from patients with drug-induced liver injury and is negatively correlated with mitochondrial mass marker TOM20. Delivery of shRNA targeting Zhx2 effectively protects mice from CCl4-induced liver injury. Together, our data clarify ZHX2 as a negative regulator of mitochondrial OXPHOS and a potential target for developing strategies for improving liver recovery after acute injuries.

Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.

Macrophages are usually educated to tumor-associated macrophages (TAMs) in cancer with pro-tumor functions by tumor microenvironment (TME) and TAM reprogramming has been proposed as a potential tumor immunotherapy strategy. We recently demonstrated the critical role of Zinc-fingers and homeoboxes 2 (Zhx2) in macrophages' metabolic programming. However, whether Zhx2 is responsible for macrophage polarization and TAMs reprogramming is largely unknown. Here, we show that Zhx2 controls macrophage polarization under the inflammatory stimulus and TME. Myeloid-specific deletion of Zhx2 suppresses LPS-induced proinflammatory polarization but promotes IL-4 and TME-induced anti-inflammatory and pro-tumoral phenotypes in murine liver tumor models. Factors in TME, especially lactate, markedly decrease the expression of Zhx2 in TAMs, leading to the switch of TAMs to pro-tumor phenotype and consequent cancer progression. Notably, reduced ZHX2 expression in TAM correlates with poor survival of HCC patients. Mechanistic studies reveal that Zhx2 associates with NF-κB p65 and binds to the Irf1 promoter, leading to transcriptional activation of Irf1 in macrophages. Zhx2 functions in maintaining macrophage polarization by regulating Irf1 transcription, which may be a potential target for macrophage-based cancer immunotherapy.

Mechanistic toxicity and growth abnormalities mediated by subacute exposure to environmentally relevant levels of benzophenone-3 in clown anemonefish (Amphiprion ocellaris).

Benzophenone-3 (BP-3) is a UV filter that is ubiquitously present in the environment due to its photostability and degradation resistance and has wide applications in personal care products. BP-3 will eventually be discharged into the ocean. Studies shows BP-3 interferes with endocrine system of aquatic organisms, especially fish. However, the toxicity and mechanisms of subacute exposure of the coral reef fish to BP-3 remain elusive. Here, we exposed the one-month-old clown anemonefish to BP-3 at 1 and 10 µg/L for 14 and 28 days, respectively. After chronic exposure, the effects of BP-3 on the growth of clown anemonefish were investigated in terms of growth-related hormones, immune enzyme activity, digestive enzyme activity, transcriptional profiling of feeding- and obesity-related genes and digital RNA sequencing. The body weight in the BP-3 groups were abnormally increased (1 µg/L group in 14 days treatment and all groups in 28 days treatment), altered insulin content (28 days exposure), immune-related and digestive-related enzymatic activities. At the molecular level, BP-3 interferes with the expression of feeding- and obesity-related genes. Digital RNA sequencing analysis showed that BP-3 interferes with Kyoto encyclopedia of genes and genomes (KEGG) pathways related to growth, social behavior (learning behavior), Mitogen-Activated Protein Kinase (MAPK) signaling pathway, PI3K-Akt signaling pathway, and insulin secretion. Notably, in the insulin secretion, BP-3 induced Ca2+ up-regulation that may damage ß cells. Growth abnormalities and social behavior (learning behavior) KEGG pathway disturbances may have potential impacts on populations of clown anemonefish. Our results reveal the toxicological effects of subacute exposure to BP-3, and provides insight into the effects and mechanisms of BP-3 on clown anemonefish growth.

DNA-Compatible Conditions for the Formation of N-Methyl Peptide Bonds.

DNA-encoded libraries (DELs) are a powerful platform in drug discovery. Peptides have unique properties that make them attractive pharmaceutical candidates. N-methylation of the peptide backbone can confer beneficial properties such as increased proteolytic stability and membrane permeability. Herein, we evaluate different DEL reaction systems and report a DNA-compatible protocol for forming N-methylated amide bonds. The DNA-compatible, bis(trichloromethyl)carbonate-mediated amide coupling is efficient for the formation of N-methyl peptide bonds, which promises to increase the opportunity to identify passively cell-permeable macrocyclic peptide hits by DNA-encoded technology.

Zhx2 maintains islet ß-cell mass and function by transcriptionally regulating Pax6.

Emerging evidence shows that pancreatic ß-cell function and quality are key determinants in the progression of type 2 diabetes (T2D). The transcription factor zinc finger homeobox 2 (Zhx2) is involved in proliferation and development of multiple cells. However, the exact role of Zhx2 in ß-cells and T2D remains completely unknown. Here, we report that Zhx2 orchestrates ß-cell mass and function by regulating paired box protein pax-6 (Pax6). We found that ß-cell-specific knockout Zhx2 (Zhx2BKO) mice showed a decrease in ß-cell proliferation and glucose homeostasis. Under prediabetic and diabetic conditions, we discovered glucose intolerance in both Zhx2BKO-HFD mice and Zhx2BKO-db/db mice, with reduced ß-cell mass and insulin secretion. Mechanistically, we demonstrated that Zhx2 targeted the Pax6 promoter region (-1740∼-1563; -862∼-559; -251∼+75), enhanced promoter activity. Overall, Zhx2 maintains ß-cell function by transcriptionally regulating Pax6, which provides a therapeutic target for diabetes intervention.

Assessing stroke rehabilitation degree based on quantitative EEG index and nonlinear parameters.

The assessment of motor function is critical to the rehabilitation of stroke patients. However, commonly used evaluation methods are based on behavior scoring, which lacks neurological indicators that directly reflect the motor function of the brain. The objective of this study was to investigate whether resting-state EEG indicators could improve stroke rehabilitation evaluation. We recruited 68 participants and recorded their resting-state EEG data. According to Brunnstrom stage, the participants were divided into three groups: severe, moderate, and mild. Ten quantitative electroencephalographic (QEEG) and five non-linear parameters of resting-state EEG were calculated for further analysis. Statistical tests were performed, and the genetic algorithm-support vector machine was used to select the best feature combination for classification. We found the QEEG parameters show significant differences in Delta, Alpha1, Alpha2, DAR, and DTABR (P < 0.05) among the three groups. Regarding nonlinear parameters, ApEn, SampEn, Lz, and C0 showed significant differences (P < 0.05). The optimal feature classification combination accuracy rate reached 85.3%. Our research shows that resting-state EEG indicators could be used for stroke rehabilitation evaluation.

Diagnosis of tuberculous uveitis by the macrogenome of intraocular fluid: A case report and review of the literature.

BACKGROUND: Tuberculous uveitis caused by tuberculosis infection factors is common, but tuberculous uveitis caused by Mycobacterium tuberculosis found in the intraocular fluid is rare. This report describes the use of intraocular fluid in the diagnosis of tuberculous uveitis in a patient and reviews the relevant literature. CASE SUMMARY: A 24-year-old woman who was 31-wk pregnant visited Hebei Chest Hospital due to intermittent chest pain, fever, and decreased vision for 3 mo. The hydrothorax test suggested "tuberculous pleurisy", and yellow effusion was extracted from the chest tube twice resulting in a total volume of approximately 800 mL. The patient chose to continue the pregnancy without treatment, and was hospitalized again due to high fever. Following 2 mo of anti-tuberculosis treatment, a healthy boy was delivered by cesarean section. Tuberculous uveitis was diagnosed using tuberculosis Xpert, and intraocular infection was detected by second-generation gene sequencing. Following systemic treatment, the patient gradually improved, and the corrected visual acuity of the left eye gradually increased from 0.08 to 1.0. CONCLUSION: The etiology of uveitis is complex, and it is necessary to assess the patient's general condition and apply molecular biology methods to determine the pathogenesis and guide precise treatment, to improve clinicians' awareness and standardize treatment of the disease.

Occurrence and Distribution of Antibiotics in a Tropical Mariculture Area of Hainan, China: Implications for Risk Assessment and Management.

With the rapid global demand for mariculture products in recent years, the use of antibiotics has increased intensively in the mariculture area. Current research on antibiotic residues in mariculture environments is limited, and less information is available on the presence of antibiotics in tropical waters, limiting a comprehensive understanding of their environmental presence and risk. Therefore, this study investigated the environmental occurrence and distribution of 50 antibiotics in the near-shore aquaculture waters of Fengjia Bay. A total of 21 antibiotics were detected in 12 sampling sites, including 11 quinolones, 5 sulfonamides, 4 tetracyclines, and 1 chloramphenicol; the quinolones pyrimethamine (PIP), delafloxacin (DAN), flurofloxacin (FLE), ciprofloxacin (CIP), norfloxacin (NOR), pefloxacin (PEF), enrofloxacin (ENO), and minocycline (MNO) of the tetracycline class were detected in all sampling points. The total antibiotic residue concentrations in the study area ranged from 153.6 to 1550.8 ng/L, the tetracycline antibiotics were detected in the range of 10 to 1344.7 ng/L, and the chloramphenicol antibiotics were detected in the range of 0 to 106.9 ng/L. The detected concentrations of quinolones ranged from 81.3 to 136.1 ng/L, and the residual concentrations of sulfonamide antibiotics ranged from 0 to 313.7 ng/L. The correlation analysis with environmental factors revealed that pH, temperature, conductivity, salinity, NH3--N, and total phosphorus had a strong correlation with antibiotics. Based on PCA analysis, the main sources of antibiotic pollution in the area were determined to be the discharge of farming wastewater and domestic sewage. The ecological risk assessment indicated that the residual antibiotics in the water environment of the near-shore waters of Fengjiawan had certain risks to the ecosystem. Among them, CIP, NOR, sulfamethoxazole (TMP), ofloxacin (OFL), enrofloxacin (ENO), sulfamethoxazole (SMX), and FLE showed medium to high risk. Therefore, it is recommended to regulate the use of these antibiotics and the discharge and treatment of culturing wastewater, and measures should be taken to reduce the environmental pollution caused by antibiotics and to monitor the long-term ecological risk of antibiotics in the region. Overall, our results provide an important reference for understanding the distribution and ecological risk of antibiotics in Fengjiawan.

Highly Diastereoselective One-Pot Synthesis of 4,5-Dihydrofuro[2,3-b]azocin-6-one Derivatives through Cyclization/[4+4] Annulation Reactions.

A variety of 4,5-dihydrofuro[2,3-b]azocin-6-one derivatives were expediently assembled through Au(I)-catalyzed cyclization and 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (BTMG)-mediated [4+4] annulation reactions of enyne-amides and ynones. The reactions exhibit high efficiency with excellent regio- and diastereoselectivity. A broad spectrum of substrates was utilized. The products with an eight-membered ring might be useful in biological chemistry and medicinal science. Furthermore, the products could be facilely converted into various derivatives.

Lipophagy-mediated cholesterol synthesis inhibition is required for the survival of hepatocellular carcinoma under glutamine deprivation.

Glutamine is critical for tumor progression, and restriction of its availability is emerging as a potential therapeutic strategy. The metabolic plasticity of tumor cells helps them adapting to glutamine restriction. However, the role of cholesterol metabolism in this process is relatively unexplored. Here, we reported that glutamine deprivation inhibited cholesterol synthesis in hepatocellular carcinoma (HCC). Reactivation of cholesterol synthesis enhanced glutamine-deprivation-induced cell death of HCC cells, which is partially duo to augmented NADPH depletion and lipid peroxidation. Mechanistically, glutamine deprivation induced lipophagy to transport cholesterol from lipid droplets (LDs) to endoplasmic reticulum (ER), leading to inhibit SREBF2 maturation and cholesterol synthesis, and maintain redox balance for survival. Glutamine deprivation decreased mTORC1 activity to induce lipophagy. Importantly, administration of U18666A, CQ, or shTSC2 viruses further augmented GPNA-induced inhibition of xenograft tumor growth. Clinical data supported that glutamine utilization positively correlated with cholesterol synthesis, which is associated with poor prognosis of HCC patients. Collectively, our study revealed that cholesterol synthesis inhibition is required for the survival of HCC under glutamine-restricted tumor microenvironment.

SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis.

Sorafenib resistance limits its survival benefit for treatment of hepatocellular carcinoma (HCC). Cholesterol metabolism is dysregulated in HCC, and its role in sorafenib resistance of HCC has not been fully elucidated. Aiming to elucidate this, in vitro and in vivo sorafenib resistant models were established. Sterol regulatory element binding transcription factor 2 (SREBF2), the key regulator of cholesterol metabolism, was activated in sorafenib resistant HepG2 and Huh7 cells. Knockdown of SREBF2 resensitized sorafenib resistant cells and xenografts tumors to sorafenib. Further study showed that SREBF2 positively correlated with StAR related lipid transfer domain containing 4 (STARD4) in our sorafenib resistant models and publicly available datasets. STARD4, mediating cholesterol trafficking, not only promoted proliferation and migration of HepG2 and Huh7 cells, but also increased sorafenib resistance in liver cancer. Mechanically, SREBF2 promoted expression of STARD4 by directly binding to its promoter region, leading to increased mitochondrial cholesterol levels and inhibition of mitochondrial cytochrome c release. Importantly, knockdown of SREBF2 or STARD4 decreased mitochondrial cholesterol levels and increased mitochondrial cytochrome c release, respectively. Moreover, overexpression of STARD4 reversed the effect of SREBF2 knockdown on mitochondrial cytochrome c release and sorafenib resistance. In conclusion, SREBF2 promotes STARD4 transcription, which in turn contributes to mitochondrial cholesterol transport and sorafenib resistance in HCC. Therefore, targeting the SREBF2-STARD4 axis would be beneficial to a subset of HCC patients with sorafenib resistance.

NAD + salvage governs mitochondrial metabolism, invigorating natural killer cell antitumor immunity.

BACKGROUND AND AIMS: Natural killer (NK) cells are key players in tumor immunosurveillance, and metabolic adaptation manipulates their fate and functional state. The nicotinamide adenine dinucleotide (NAD + ) has emerged as a vital factor to link cellular metabolism and signaling transduction. Here, we identified NAD + metabolism as a central hub to determine the homeostasis and function of NK cells. APPROACH AND RESULTS: NAD + level was elevated in activated NK cells. NAD + supplementation not only enhanced cytokine production and cytotoxicity but also improved the proliferation and viability of NK cells. Intriguingly, the salvage pathway was involved in maintaining NAD + homeostasis in activated NK cells. Genetic ablation or pharmacological blockade of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD + salvage pathway, markedly destroyed the viability and function of NK cells. Mechanistically, NAD + salvage dictated the mitochondrial homeostasis and oxidative phosphorylation activity to support the optimal function of NK cells. However, in human HCC tissues, NAMPT expression and NAD + level were significantly down-regulated in tumor-infiltrating NK cells, which negatively correlated with patient survival. And lactate accumulation in the tumor microenvironment was at least partially responsible for the transcriptional repression of NAMPT in NK cells. Further, deficiency of Nampt in NK cells accelerated the growth of HCC and melanoma. Supplementation of the NAD + precursor nicotinamide mononucleotide (NMN) significantly improved NK antitumor response in both mouse and human cell-derived xenografts. CONCLUSIONS: These findings reveal NAD + salvage as an essential factor for NK-cell homeostasis and function, suggesting a potential strategy for invigorating NK cell-based immunotherapy.

Application of metagenomic next-generation sequencing in suspected intraocular infections.

PURPOSE: To evaluate the efficacy of metagenomic next-generation sequencing (mNGS) and to explore its value in the diagnosis of intraocular infection. METHODS: A retrospective case-series study of patients with suspected intraocular infection was performed. Intraocular fluid samples were collected from all the patients and sent for mNGS. Detailed clinical data, the results of mNGS and other laboratory examinations, the sequencing data of mNGS, and the final diagnosis were recorded. RESULTS: Fifteen eyes of 15 patients were included in the study. Eight samples were identified as positive for different kinds of pathogens by mNGS, which were all confirmed by other laboratory examinations or effective diagnostic treatment. The mNGS results were negative in seven samples. The final diagnosis was still intraocular infection in four of the seven negative results. Of these, one patient was diagnosed with fungal endophthalmitis according to the clinical characteristics and good treatment response to the anti-fungal therapy, one patient underwent vitrectomy and the bacterial culture of the vitreous sample was positive for Brucella melitensis, and two patients were diagnosed with ocular tuberculosis according to the positive T-SPOT test and effective anti-tuberculous treatments. CONCLUSIONS: mNGS could be helpful in determining pathogens in cases of suspected intraocular infection. The mNGS protocols should be optimized for the detection of intracellular bacterial and fungal pathogens.

Environmental concentrations of benzophenone-3 disturbed lipid metabolism in the liver of clown anemonefish (Amphiprion ocellaris).

Benzophenone-3 (BP-3) often used as a UV filter in various products and an endocrine disruptor. In this work, we exposed the clown anemonefish to 10 µg/L and 50 µg/L BP-3 for 7 and 14 days. Liver histological, biochemical analysis, and transcriptome sequencing were used to explore the mechanism of the lipid metabolism disorder in the liver of three-month-old clown anemonefish treated with BP-3. The histological and biochemical analysis showed that BP-3 induces morphological changes and lipid droplet accumulation, and the lipid content, lipase, and antioxidant enzyme activity were abnormal. After treatment with 10 µg/L and 50 µg/L BP-3 for 7 days, the transcriptome analysis further demonstrated that the KEGG analysis revealed that the differentially expressed genes (DEGs) were mainly associated with fat digestion and absorption, PPAR signaling pathway, circadian rhythm, and mineral absorption pathways; After 10 µg/L and 50 µg/L of BP-3 exposure for 14 days, the KEGG analysis were mainly associated with circadian rhythm, circadian rhythm-fly, protein processing in the endoplasmic reticulum, and beta-alanine metabolism pathways. Several key genes were involved in the process of liver lipid metabolism, including CD36, APoA-Ⅰ, FABP, LPL, ACS, and PEPCK. The qRT-PCR validation results showed that eight genes (CYP8B1, FABP1, LPL, MGAT, PEPCK, PER1, PSMB4, PSME2) were significantly down-regulated, and the other two genes (Fbxl3, RXR) were significantly up-regulated after 7 days of BP-3 exposure. Similarly, eleven genes (AMPK, ARNTL, Bmal1, CASP3, CYC, CYP2J, CYP2U1, GSK3A, PEPCK, RAC1, RORA) were significantly up-regulated, and the other four genes (NR1D1, PER1, PTGDS, HLF) were significantly down-regulated after 14 days of BP-3 exposure. In conclusion, our results elucidate the physiological and molecular responses to BP-3 exposure in the liver lipid metabolism of clown anemonefish, and these findings reveal that the regulation of lipid metabolism is disturbed when clown anemonefish is exposed to UV filters.