High-grade serous papillary ovarian carcinoma combined with nonkeratinizing squamous cell carcinoma of the cervix: a case report.

Multiple primary malignant neoplasms are a rare gynecologic malignancy; particularly, cases originating from the heterologous organs, such as the ovary and cervix. Here, we report a case of two primary malignant neoplasms in a patient who had undergone laparoscopic radical hysterectomy + bilateral salpingo-oophorectomy + pelvic lymph node dissection + para-aortic lymphadenectomy + appendectomy + omentectomy + metastasectomy under general anesthesia. The patient experienced complete remission after six courses of postoperative chemotherapy with a standard Taxol and Carboplatin regimen. Genetic testing was performed to detect BRCA2 mutations, and poly (ADP-ribose) polymerase (PARP) inhibitors were used for maintenance therapy.

In vitro osteoclastogenesis assessment using murine myeloid-derived suppressor cells.

The study of myeloid-derived suppressor cells (MDSCs) has been commonly reported in the context of cancer immunology. MDSCs play a key role in cancer growth and progression by inhibiting both innate and adaptive immunity. In addition to the immunosuppressive function of MDSCs in cancer, a novel function of MDSCs as osteoclast precursors has recently been attracting attention. Because monocytic-MDSCs (M-MDSCs) are derived from the same myeloid lineage as macrophages, which are osteoclast progenitors, M-MDSCs can undergo differentiation into osteoclasts, contributing to bone destruction not only in the cancer microenvironment but also in inflammatory conditions including obesity and osteoarthritis. Herein, we present details of the technique to evaluate osteoclasts in vitro, as well as specific techniques to isolate M-MDSCs and identify them. This protocol can be easily adapted to isolate M-MDSCs from most pathologic conditions for easy evaluation.

Neuropilin-1 enhances temozolomide resistance in glioblastoma via the STAT1/p53/p21 axis.

Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.

Multi-Omics Research Accelerates the Clarification of the Formation Mechanism and the Influence of Leaf Color Variation in Tea (Camellia sinensis) Plants.

Tea is a popular beverage with characteristic functional and flavor qualities, known to be rich in bioactive metabolites such as tea polyphenols and theanine. Recently, tea varieties with variations in leaf color have been widely used in agriculture production due to their potential advantages in terms of tea quality. Numerous studies have used genome, transcriptome, metabolome, proteome, and lipidome methods to uncover the causes of leaf color variations and investigate their impacts on the accumulation of crucial bioactive metabolites in tea plants. Through a comprehensive review of various omics investigations, we note that decreased expression levels of critical genes in the biosynthesis of chlorophyll and carotenoids, activated chlorophyll degradation, and an impaired photosynthetic chain function are related to the chlorina phenotype in tea plants. For purple-leaf tea, increased expression levels of late biosynthetic genes in the flavonoid synthesis pathway and anthocyanin transport genes are the major and common causes of purple coloration. We have also summarized the influence of leaf color variation on amino acid, polyphenol, and lipid contents and put forward possible causes of these metabolic changes. Finally, this review further proposes the research demands in this field in the future.

Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Decision Impact Analysis to Measure the Influence of Molecular Signature Response Classifier Testing on Treatment Selection in Rheumatoid Arthritis.

INTRODUCTION: Clinical guidelines offer little guidance for treatment selection following inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARD) in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) was validated to predict tumor necrosis factor inhibitor (TNFi) inadequate response. The decision impact of MSRC results on biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) selection was evaluated. METHODS: This is an analysis of AIMS, a longitudinal, prospective database of patients with RA tested using the MSRC. This study assessed selection of b/tsDMARDs class after MSRC testing by surveying physicians, the rate of b/tsDMARD prescriptions aligning with MSRC results, and the percentage of physicians utilizing MSRC results for decision-making. RESULTS: Of 1018 participants, 70.7% (720/1018) had treatment selected after receiving MSRC results. In this MSRC-informed cohort, 75.6% (544/720) of patients received a b/tsDMARD aligned with MSRC results, and 84.6% (609/720) of providers reported using MSRC results to guide treatment selection. The most prevalent reason reported (8.2%, 59/720) for not aligning treatment selection with MSRC results from the total cohort was health insurance coverage issues. CONCLUSION: This study showed that rheumatologists reported using the MSRC test to guide b/tsDMARD selection for patients with RA. In most cases, MSRC test results appeared to influence clinical decision-making according to physician self-report. Wider adoption of precision medicine tools like the MSRC could support rheumatologists and patients in working together to achieve optimal outcomes for RA.

Intervention with extracellular matrix metalloproteinase inducer in osteoclasts attenuates periodontitis-induced bone resorption.

Extracellular matrix metalloproteinase inducer (EMMPRIN) plays critical roles in the regulation of inflammation and bone metabolism. The roles of EMMPRIN signaling in osteoclasts are worthy of deep study. The present study aimed to investigate bone resorption in periodontitis through the intervention of EMMPRIN signaling. The distribution of EMMPRIN in human periodontitis was observed. RANKL-induced osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) were treated with EMMPRIN inhibitor in vitro. Rats with ligation-induced periodontitis were treated with EMMPRIN inhibitor and harvested for microcomputed tomography scanning, histologic observation, immunohistochemistry, and double immunofluorescence analysis. Positive expressions of EMMPRIN could be found in the CD68+-infiltrating cells. Downregulated EMMPRIN restrained osteoclast differentiation of BMMs in vitro, which also inhibited MMP-9 expression (*P < 0.05). In vivo, EMMPRIN inhibitor restrained ligation-induced bone resorption by decreasing tartrate-resistant acid phosphatase-positive osteoclasts. Both EMMPRIN-positive and MMP-9-positive osteoclasts were less common in the EMMPRIN inhibitor groups than in the control groups. Intervention of EMMPRIN signaling in osteoclasts could probably provide a potential therapeutic target for attenuating ligation-induced bone resorption.

7-Methoxy-13-dehydroxypaxilline: New indole diterpenoid from an endophytic fungus Penicillium sp. Nb 19.

ABSTACTA chemical investigation of the endophyte Penicillium sp. Nb 19, isolated from leaves of the traditionally medical plant Baphicacanthus cusia (Nees) Bremek., yielded one new indole diterpenoid, 7-methoxy-13-dehydroxypaxilline (1) together with seven known metabolites (2-8). The obtained structure of compound 1 was elucidated by its spectroscopic data. In addition, the absolute configuration of compound 6 was confirmed by ECD for the first time. Compounds 1-6 were evaluated for antitumor activity against MCF-7, HepG2, and HCCC-9810 cell lines.

HOMER3 promotes non-small cell lung cancer growth and metastasis primarily through GABPB1-mediated mitochondrial metabolism.

Cancer metabolism has emerged as a major target for cancer therapy, while the state of mitochondrial drugs has remained largely unexplored, partly due to an inadequate understanding of various mitochondrial functions in tumor contexts. Here, we report that HOMER3 is highly expressed in non-small cell lung cancer (NSCLC) and is closely correlated with poor prognosis. Lung cancer cells with low levels of HOMER3 are found to show significant mitochondrial dysfunction, thereby suppressing their proliferation and metastasis in vivo and in vitro. At the mechanistic level, we demonstrate that HOMER3 and platelet-activating factor acetylhydrolase 1b catalytic subunit 3 cooperate to upregulate the level of GA-binding protein subunit beta-1 (GABPB1), a key transcription factor involved in mitochondrial biogenesis, to control mitochondrial inner membrane genes and mitochondrial function. Concurrently, low levels of HOMER3 and its downstream target GABPB1 led to mitochondrial dysfunction and decreased proliferation and invasive activity of lung cancer cells, which raises the possibility that targeting mitochondrial synthesis is an important and promising therapeutic approach for NSCLC.

Perioperative care of nipple-areola complex-sparing mastectomy and one-stage breast reconstruction via endoscopic axillary approach for ductal carcinoma in situ: A case report.

RATIONALE: Breast cancer represents a prevalent malignancy that primarily impacts women, with pronounced consequences on their overarching health. The major therapeutic approach, encompassing surgical procedures, can often culminate in mastectomy, potentially inciting psychological turmoil and disorders. PATIENT CONCERNS: A patient was admitted to our facility on May 5, 2023, precipitated by the discovery of bilateral breast masses during a routine physical examination conducted 3 days before admission. DIAGNOSIS: The breasts were symmetric, with the right nipple inverted and a palpable mass in the upper outer quadrant of the right breast, measuring approximately 5 cm × 4 cm. The mass was firm with indistinct borders, relatively regular morphology, poor mobility, and no tenderness. Outpatient color Doppler ultrasound revealed heterogeneous echogenicity in the right breast, classified as Breast Imaging Reporting and Data System (BI-RADS) category 0, along with multiple ductal dilatations. The left breast exhibited a hypoechoic area (BI-RADS 3), indicative of proliferative changes. Radiographic mammography confirmed diffuse changes in the right breast (BI-RADS 0) and proliferative signs in the left breast (BI-RADS 2). Biopsy results reveal significant atypical ductal hyperplasia consistent with intermediate-grade ductal carcinoma in situ. This patient was diagnosed as ductal carcinoma in situ of the right breast (cTisN0M0 and Stage 0), accompanied by a left breast mass. INTERVENTIONS: On May 15, 2023, the patient was readmitted for further surgical intervention. Following relevant auxiliary examinations, the patient underwent nipple-areola complex-sparing radical mastectomy for the right breast, sentinel lymph node biopsy in the right axillary area, prosthesis-based breast reconstruction for the right breast, and microrotatotomy of the left breast mass on the left side on May 17. OUTCOMES: The patient made a successful recovery under scrupulous perioperative supervision and was discharged 7 days post-surgery. LESSONS: The axillary approach for endoscopic mammary gland excision and immediate implant reconstruction permits patients to preserve the esthetics of the female form while undergoing conventional medical treatment. This methodology considerably enhances the psychophysical health of the patients, thereby marking it as an advantageous practice worthy of broad dissemination in the medical community.

M4IDP stimulates ROS elevation through inhibition of mevalonate pathway and pentose phosphate pathway to inhibit colon cancer cells.

Maintaining redox homeostasis is an essential feature of cancer cells, and disrupting this homeostasis to cause oxidative stress and induce cell death is an important strategy in cancer therapy. M4IDP, a zoledronic acid derivative, can cause the death of human colorectal cancer cells by increasing the level of intracellular reactive oxygen species (ROS). However, its potential molecular mechanism is unclear. Our in vitro studies showed that treatment with M4IDP promoted oxidative stress in HCT116 cells, as measured by the decreased ratios of GSH/GSSG and NADPH/NADP+ and increased level of MDA. M4IDP could cause the decrease of GSH content, the increase of GSSG content, the decrease of NADPH content and pentose phosphate pathway flux, the downregulation of G6PD expression, the upregulation of unprenylated Rap1A and total expression of RhoA and CDC42. The increase of ROS and cytotoxicity induced by M4IDP could be reversed by the supplementation of NADPH, the overexpression of G6PD and the supplementation of GGOH. In vivo studies showed that M4IDP inhibited tumor growth in the human colorectal cancer xenograft mouse model, which was accompanied with a decreased [18F]FDG uptake. Collectively, these results provide evidence that M4IDP can promote oxidation in colon cancer cells by inhibiting mevalonate pathway and pentose phosphate pathway and produce therapeutic effect. This study revealed for the first time a possible mechanism of bisphosphonate-induced increase of ROS in malignant tumor cells. This is helpful for the development of new molecular therapeutic targets and can provide new ideas for the combined therapy of bisphosphonates in tumors.

Hexavalent chromium caused DNA damage repair and apoptosis via the PI3K/AKT/FOXO1 pathway triggered by oxidative stress in the lung of rat.

Hexavalent chromium [Cr(VI)] is an occupational carcinogen that accumulates in the lungs and causes lung injury and even lung cancer. 36 SD male rats received inhalable intratracheal instillation of Cr(VI) (0.05, 0.25 mg Cr/kg) or the same volume (3 ml/kg) of normal saline weekly for 28 days (total 5 times). After 28 days of exposure, half of the rats in each group were sacrificed for investigation, and the rest stopped exposure and began to be self-repaired for two weeks. Histopathology analyses revealed that Cr(VI) induced slight dilatation and hemorrhage of perialveolar capillaries, pulmonary bronchodilation, and congestion with peripheral flaky-like necrosis accompanied by inflammatory cell infiltration, especially the 0.25 mg Cr/kg group. Cr(VI) exposure caused the increase of blood Cr, urinary Cr, MDA, urinary 8-hydroxy-2' -deoxyguanosine (8-OHdG), and the decrease of GSH and MDA, while two-week repair only reduced urinary Cr. Exposure to Cr(VI) significantly upregulated FOXO1 and downregulated p-AKT and p-FOXO1 for two weeks. PI3K in the 0.25 mg Cr/kg group was inhibited after two weeks of repair. Cr(VI) exposure mainly promoted GADD45a and CHK2 in the exposure group, promoted Bim, Bax/Bcl-2, and suppressed Bcl-2 and Bcl-xL in the repair group. These results demonstrate that Cr(VI) may induce DNA damage repair and apoptosis in the lung by activating the PI3K/AKT/FOXO1 pathway. Two-week repair may alleviate oxidative stress and DNA damage induced by Cr(VI) exposure but couldn't eliminate its effects. This study provides a new perspective for exploring the Cr(VI) induced lung cancer mechanism.

Preparation and anti-triple-negative breast cancer cell effect of a nanoparticle for the codelivery of paclitaxel and gemcitabine.

Amphiphilic polymers (HA-ANI) were prepared by grafting hyaluronic acid (HA) and 6-(2-nitroimidazole)hexylamine (ANI) and then self-assemble in water to form nanoparticles (NPs) that could be loaded with paclitaxel (PTX) and gemcitabine (GEM) by dialysis. Infrared spectroscopy and 1H-NMR indicated the successful synthesis of HA-ANI. Three different ratios of NPs were prepared by adjusting the ratios of hydrophilic and hydrophobic materials, and the particle size decreased as the ratio of hydrophilic materials increased. When HA:ANI = 2.0:1, the nanoparticles had the smallest size distribution, good stability and near spherical shape and had high drug loading and encapsulation rates. In vitro release experiments revealed that NADPH could accelerate the drug release from NPs. Cellular uptake rate reached 86.50% at 6 h. The toxic effect of dual drug-loaded nanoparticles (P/G NPs) on MDA-MB-231 cells at 48 h was stronger than that of the free drug. The AO/EB double-staining assay revealed that a large number of late apoptotic cells appeared in the P/G NPs group, and the degree of cell damage was significantly stronger than that of the free drug group. In the cell migration assay, the 24 h-cell migration rate of the P/G NPs group was 5.99%, which was much lower than that of the free group (13.87% and 17.00%). In conclusion, MDA-MB-231 cells could effectively take up P/G NPs, while the introduction of the nano-codelivery system could significantly enhance the toxicity of the drug to MDA-MB-231 cells as well as the migration inhibition effect.

GPRC5A regulates proliferation and oxidative stress by inhibiting the STAT3/Socs3/c-MYC pathway in hepatocellular carcinoma.

The G protein-coupled receptor, class C, group 5, member A (GPRC5A) plays a key role in various diseases, but its effect on hepatocellular carcinoma (HCC) and the potential underlying mechanisms remains unclear. In the present study, we explored the effect of GPRC5A on the progression of HCC and further explored its mechanism of action. The results revealed that the expression of GPRC5A was lower in HCC tissues and cells. Overexpression of GPRC5A suppressed the proliferation and epithelial-mesenchymal transition (EMT) of HCC cells. In addition, overexpression of GPRC5A induced oxidative stress and apoptosis. Further study showed that overexpression of GPRC5A inhibited the expression of STAT3/Socs3/c-MYC related-protein and the NLRP3 inflammasome. Moreover, the STAT3/Socs3/c-MYC and NLRP3 inflammasome was involved in the effect of GPRC5A on HCC cells. These results suggest that GPRC5A suppresses proliferation and EMT, induces oxidative stress and leads to apoptosis of HCC cells, potentially by regulating STAT3/Socs3/c-MYC signalling and the NLRP3 inflammasome. These findings suggest that GPRC5A has an anti-tumor effect in the formation of HCC, and the molecular therapy of GPRC5A provides a theoretical basis for treating HCC.

Preparation and Bioevaluation of 18F-Labeled Small-Molecular Radiotracers via Sulfur(VI) Fluoride Exchange Chemistry for Imaging of Programmed Cell Death Protein Ligand 1 Expression in Tumors.

Nowadays, one of the most effective methods of tumor immunotherapy is blocking programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) immune checkpoints. However, there is still a significant challenge in selecting patients to benefit from immune checkpoint therapies. Positron emission tomography (PET), a noninvasive molecular imaging technique, offers a new approach to accurately detect PD-L1 expression and allows for a better prediction of response to PD-1/PD-L1 target immunotherapy. Here, we designed and synthesized a novel group of aryl fluorosulfate-containing small-molecule compounds (LGSu-1, LGSu-2, LGSu-3, and LGSu-4) based on the phenoxymethyl-biphenyl scaffold. After screening by the time-resolved fluorescence resonance energy transfer (TR-FRET) assay, the most potent compound LGSu-1 (half maximal inhibitory concentration (IC50): 15.53 nM) and the low-affinity compound LGSu-2 (IC50: 189.70 nM) as a control were selected for 18F-radiolabeling by sulfur(VI) fluoride exchange chemistry (SuFEx) to use for PET imaging. [18F]LGSu-1 and [18F]LGSu-2 were prepared by a one-step radiofluorination reaction in over 85% radioconversion and nearly 30% radiochemical yield. In B16-F10 melanoma cell assays, [18F]LGSu-1 (5.00 ± 0.06%AD) showed higher cellular uptake than [18F]LGSu-2 (2.55 ± 0.04%AD), in which cell uptake could be significantly blocked by the nonradioactivity LGSu-1. In vivo experiments, micro-PET imaging of B16-F10 tumor-bearing mice and radiographic autoradiography of tumor sections showed that [18F]LGSu-1 was more effectively accumulated in the tumor due to the higher binding affinity with PD-L1. The above experimental results confirmed the potential of the small-molecule probe LGSu-1 as a targeting PD-L1 imaging tracer in tumor tissues.

Stacking Ensemble Learning-Based [18F]FDG PET Radiomics for Outcome Prediction in Diffuse Large B-Cell Lymphoma.

This study aimed to develop an analytic approach based on [18F]FDG PET radiomics using stacking ensemble learning to improve the outcome prediction in diffuse large B-cell lymphoma (DLBCL). Methods: In total, 240 DLBCL patients from 2 medical centers were divided into the training set (n = 141), internal testing set (n = 61), and external testing set (n = 38). Radiomics features were extracted from pretreatment [18F]FDG PET scans at the patient level using 4 semiautomatic segmentation methods (SUV threshold of 2.5, SUV threshold of 4.0 [SUV4.0], 41% of SUVmax, and SUV threshold of mean liver uptake [PERCIST]). All extracted features were harmonized with the ComBat method. The intraclass correlation coefficient was used to evaluate the reliability of radiomics features extracted by different segmentation methods. Features from the most reliable segmentation method were selected by Pearson correlation coefficient analysis and the LASSO (least absolute shrinkage and selection operator) algorithm. A stacking ensemble learning approach was applied to build radiomics-only and combined clinical-radiomics models for prediction of 2-y progression-free survival and overall survival based on 4 machine learning classifiers (support vector machine, random forests, gradient boosting decision tree, and adaptive boosting). Confusion matrix, receiver-operating-characteristic curve analysis, and survival analysis were used to evaluate the model performance. Results: Among 4 semiautomatic segmentation methods, SUV4.0 segmentation yielded the highest interobserver reliability, with 830 (66.7%) selected radiomics features. The combined model constructed by the stacking method achieved the best discrimination performance. For progression-free survival prediction in the external testing set, the areas under the receiver-operating-characteristic curve and accuracy of the stacking-based combined model were 0.771 and 0.789, respectively. For overall survival prediction, the stacking-based combined model achieved an area under the curve of 0.725 and an accuracy of 0.763 in the external testing set. The combined model also demonstrated a more distinct risk stratification than the International Prognostic Index in all sets (log-rank test, all P < 0.05). Conclusion: The combined model that incorporates [18F]FDG PET radiomics and clinical characteristics based on stacking ensemble learning could enable improved risk stratification in DLBCL.

24-Hour efficacy of single primary selective laser trabeculoplasty versus latanoprost eye drops for Naïve primary open-angle glaucoma and ocular hypertension patients.

This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps < 0.05). Compared with the SLT group, the latanoprost group had a significant and stable decrease in IOP after treatment. The latanoprost group had a more pronounced reduction in IOP at weeks 4 and 12 (P < 0.05) but had no difference at week 1 (P = 0.097). As a first-line treatment, both SLT and latanoprost eye drops are effective in newly diagnosed POAG and OHT patients. However, the latanoprost eye drops may be better in decreasing mean and peak 24-h IOP and thus controlling 24-h IOP fluctuation compared to SLT.

Simple and sensitive detection of miRNA-122 based on a micro-biosensor through square wave voltammetry.

The simple and sensitive detection of miRNA-122 in blood is crucially important for early hepatocellular carcinoma (HCC) diagnosis. In this work, a platinum microelectrode (PtµE) was prepared and electrodeposited with molybdenum disulfide (MoS2) and gold nanoparticles (AuNP), respectively, and denoted as PtµE/MoS2/Au. The prepared PtµE/MoS2/Au was used as the microsensor for the detection of miRNA-122 combined with the probe DNA as a biorecognition element which is the complementary strand of miRNA-122. The PtµE/MoS2/Au conjugated with the probe DNA modified with sulfydryl units was used as the micro-biosensor for the detection of miRNA-122. The square wave voltammetry was performed for the quantitative detection of miRNA-122 using [Fe(CN)6]4-/3- as a mediator. Under the optimized conditions, the PtµE/MoS2/Au micro-biosensor shows a linear detection toward miRNA-122 ranging from 10-11 to 10-8 M (S = 6.9 nA dec-1, R2 = 0.9997), and the detection limit is 1.6 × 10-12 M (3σ/b). The PtµE/MoS2/Au micro-biosensor demonstrates good selectivity against other types of proteins and small molecules, and has good reproducibility. Moreover, the PtµE/MoS2/Au micro-biosensor was successfully applied for the measurement of miRNA-122 in real blood samples. Herein, the proposed detection assay could be a potential tool in HCC clinical diagnostics with high sensitivity.

Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression.

Immunotherapy blocking programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway has achieved great therapeutic effect in the clinic, but the overall response rate is not satisfactory. Early studies showed that response to treatment and overall survival could be positively related to PD-L1 expression in tumors. Therefore, accurate measurement of PD-L1 expression will help to screen cancer patients and improve the overall response rate. A small molecular positron emission tomography (PET) probe [18F]LP-F containing a biphenyl moiety was designed and synthesized for measurement of PD-L1 expression in tumors. The PET probe [18F]LP-F was obtained with a radiochemical yield of 12.72 ± 1.98%, a radiochemical purity of above 98% and molar activity of 18.8 GBq/µmol. [18F]LP-F had good stability in phosphate buffer saline (PBS) and mouse serum. In vitro assay indicated that [18F]LP-F showed moderate affinity to PD-L1. Micro-PET results showed that the tumor accumulation of [18F]LP-F in A375 tumor was inferior to that in A375-hPD-L1 tumor. All the results demonstrated that [18F]LP-F could specifically bind to PD-L1 and had a potential application in non-invasive evaluation of PD-L1 expression in tumors.

Modulation of gut microbiota alleviates cerebral ischemia/reperfusion injury in rats by inhibiting M1 polarization of microglia.

Gut microbiota affects the gut-brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO/R or sham surgery, and then they received FMT (started 3 days later; continued for 10 days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers-TNF-α, IL-1ß, IL-6, and iNOS-in the rats following MCAO/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16 S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO/R animals. In contrast, FMT reversed this MCAO/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-κB pathways, which reversed the M2-to-M1 microglial shift 10 days after MCAO/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-κB pathways. However, an understanding of the underlying mechanism requires further study.