In situ structure of the red algal phycobilisome-PSII-PSI-LHC megacomplex.

In oxygenic photosynthetic organisms, light energy is captured by antenna systems and transferred to photosystem II (PSII) and photosystem I (PSI) to drive photosynthesis1,2. The antenna systems of red algae consist of soluble phycobilisomes (PBSs) and transmembrane light-harvesting complexes (LHCs)3. Excitation energy transfer pathways from PBS to photosystems remain unclear owing to the lack of structural information. Here we present in situ structures of PBS-PSII-PSI-LHC megacomplexes from the red alga Porphyridium purpureum at near-atomic resolution using cryogenic electron tomography and in situ single-particle analysis4, providing interaction details between PBS, PSII and PSI. The structures reveal several unidentified and incomplete proteins and their roles in the assembly of the megacomplex, as well as a huge and sophisticated pigment network. This work provides a solid structural basis for unravelling the mechanisms of PBS-PSII-PSI-LHC megacomplex assembly, efficient energy transfer from PBS to the two photosystems, and regulation of energy distribution between PSII and PSI.

Structural basis of energy transfer in Porphyridium purpureum phycobilisome.

Photosynthetic organisms have developed various light-harvesting systems to adapt to their environments1. Phycobilisomes are large light-harvesting protein complexes found in cyanobacteria and red algae2-4, although how the energies of the chromophores within these complexes are modulated by their environment is unclear. Here we report the cryo-electron microscopy structure of a 14.7-megadalton phycobilisome with a hemiellipsoidal shape from the red alga Porphyridium purpureum. Within this complex we determine the structures of 706 protein subunits, including 528 phycoerythrin, 72 phycocyanin, 46 allophycocyanin and 60 linker proteins. In addition, 1,598 chromophores are resolved comprising 1,430 phycoerythrobilin, 48 phycourobilin and 120 phycocyanobilin molecules. The markedly improved resolution of our structure compared with that of the phycobilisome of Griffithsia pacifica5 enabled us to build an accurate atomic model of the P. purpureum phycobilisome system. The model reveals how the linker proteins affect the microenvironment of the chromophores, and suggests that interactions of the aromatic amino acids of the linker proteins with the chromophores may be a key factor in fine-tuning the energy states of the chromophores to ensure the efficient unidirectional transfer of energy.

Comparison of three-dimensional heads-up system versus traditional microscopic system in medical education for vitreoretinal surgeries: a prospective study.

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.

Analysis of barriers associated with emergency medical service activation in patients with acute stroke and acute myocardial infarction from Zhongjiang County of Sichuan Province in China.

OBJECTIVES: The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances. METHODS: We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people's hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression. RESULTS: we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient's son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient's partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use. CONCLUSION: There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities.

Human Adipose-Derived Microvessel Fragments: A Natural Vascularization Units for Ischemic Diseases.

BACKGROUND: In plastic surgery tissue transplantation, tissue ischemia limits transplanted tissue survival. Adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) show potential for promoting angiogenesis and rescuing ischemic conditions. However, when SVF and ASC suspensions are utilized without the protection of extracellular matrix, the retention rate of transplanted cells tends to be diminished, leading to an unsatisfactory therapeutic outcome. To overcome this, adipose tissue-derived microvascular fragments (ad-MVFs) have emerged as a promising solution. METHODS: We conducted enzymatic digestion on human adipose tissue to generate ad-MVFs. These fragments underwent a thorough characterization process, utilizing electron microscopy to assess their structural attributes and enabling a detailed analysis of their intricate morphology. Furthermore, our team investigated the cellular composition of these microvascular fragments, subsequently confirming their ability to enhance the viability of ischemic skin flaps. RESULTS: The resulting product primarily comprised fragments with sizes ranging from 20 to 50 µm, and some exhibited a sophisticated network-like structure. Electron microscopy examination revealed the presence of collagen components in the product. Additionally, flow cytometry analysis indicated a substantial abundance of adipose-derived stem cells and endothelial cells within these microvascular fragments. Significantly, when tested in treating an ischemic skin flap in a nude mouse model, the product exhibited superior therapeutic efficacy compared to SVF cell suspension. CONCLUSION: We have successfully generated human ad-MVFs and established standardized procedures. Compared with SVF, Ad-MVFs have a better effect in the treatment of ischemic diseases. LEVEL OF EVIDENCE II: 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sjögren's Syndrome.

Objective As primary Sj?gren's syndrome (pSS) primarily affects the salivary glands, saliva can serve as an indicator of the glands' pathophysiology and the disease's status. This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis.Methods The discovery set contained 49 samples (24 from pSS and 25 from age- and gender-matched healthy controls [HCs]) and the validation set included 25 samples (12 from pSS and 13 from HCs). Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio. Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition (DIA) strategy on a 2D LC?HRMS/MS platform to reveal differential proteins. The crucial proteins were verified using DIA analysis and annotated using gene ontology (GO) and International Pharmaceutical Abstracts (IPA) analysis. A prediction model for SS was established using random forests.Results A total of 1,963 proteins were discovered, and 136 proteins exhibited differential representation in pSS patients. The bioinformatic research indicated that these proteins were primarily linked to immunological functions, metabolism, and inflammation. A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm, and was validated as the predictive biomarkers exhibiting good performance with area under the curve (AUC) of 0.817 for discovery set and 0.882 for validation set.Conclusions The candidate protein panel discovered may aid in pSS diagnosis. Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients. DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Application of next-generation sequencing in the detection of low-abundance mutations.

Mutation accumulation in somatic cells contributes to cancer development, aging and many non-malignant diseases. The true mutation frequency in normal cells is extremely low, which presents a challenge in detecting these mutations at such low frequencies. The emergence of next-generation sequencing (NGS) technology enables direct detection of rare mutations across the entire genome of any species. This breakthrough overcomes numerous limitations of traditional mutation detection techniques that rely on specific detection models and sites. However, conventional NGS is limited in its application for detecting low-frequency mutations due to its high sequencing error rate. To address this challenge, high-accuracy NGS sequencing techniques based on molecular consensus sequencing strategies have been developed. These techniques have the ability to correct sequencing errors, resulting in error rates lower than 10-7, are expected to serve as effective tools for low-frequency mutation detection. Error-corrected NGS (ecNGS) techniques hold great potential in various areas, including safety evaluation and research on environmental mutagens, risk assessment of cell and gene therapy drugs, population health risk monitoring, and fundamental research in life sciences. This review highlights a comprehensive review of the research progress in low-frequency mutation detection techniques based on NGS, and provides a glimpse into their potential applications. It also offers an outlook on the potential applications of these techniques, thereby providing valuable insights for further development, research, and application of this technology in relevant fields.

O-Glycopeptide Truncation Strategy for Heterogeneous O-GalNAc Glycoproteomics Characterization.

Mucin-type O-glycosylation (or O-GalNAcylation) takes place on most membrane and secretory proteins and is vital in regulating protein functions and many biological processes. O-GalNAcylation generally exhibits highly diverse and dense O-glycans linked to carrier proteins, which challenges the analysis of O-GalNAc glycoproteome using conventional methodologies. Here, we report an O-glycopeptide truncation strategy for the characterization of protein O-GalNAcylation in biological samples. The O-glycopeptide truncation strategy utilizes proteases or O-glycopeptidases for targeted cleavage of the enriched tryptic O-glycopeptides. It simplifies the O-glycopeptide backbones, O-glycans, or both, and has been shown to aid the improvement of the analytical coverage of O-GalNAc glycopeptides and glycoproteins. Tryptic O-glycopeptides covered with O-glycan clusters and terminal sialic acids could be well isolated by the hydrophilic-based enrichment approaches. The enriched O-glycopeptides are then enzymatically truncated into shorter or less multiply O-glycosylated peptides, which are more favorable for mass spectrometry detection and database search in general bottom-up glycoproteomics. We also investigate different proteolysis which could be well integrated into the O-glycopeptide truncation strategy. For large-scale analysis, we exploit different truncation schemes and identify nearly 2000 O-glycopeptides corresponding to 391 glycoproteins from 75 µL human serum, achieving the deepest-scale coverage of O-glycoproteins compared to other plasma/serum O-glycoproteomic studies. Together, the O-glycopeptide truncation strategy has great potential to facilitate the in-depth study of O-GalNAc glycoproteomics in biological samples.

Temporal Tracking of Insulin Action on the Cell Surface of Proteins at a Resolution of Ten Seconds.

The ligand-receptor signaling occurring on the cell surface governs cell growth, proliferation, and survival via rapidly triggering a cascade of events. Here, we for the first time report an in situ perturbation-free and rapid surface proteomic profiling at a temporal resolution of ten seconds. By this innovation, about 1022 cell surface-associated proteins were reproducibly identified and quantified. It is noteworthy that, upon a model ligand insulin stimulus, a few rapid-responding proteins at 10 s to 2 min were identified, e.g., CNNM3. Moreover, temporal response patterns were established for the members of GLUT4 storage vesicles (GSVs; responsible for glucose transportation) and confirmed with five known GSV proteins. This pattern was then exploited to uncover seven new regulatory proteins (LDLR, HFE, ECE1, MRC2, CORO1C, CPD, and BST2). Collectively, we showed a powerful surface proteomic tool to decipher rapid signaling of cell-surface proteins and to uncover new subunits involved in rapidly trafficking vesicles.

Clinical significance of B7-H3 expression in circulating CD4+CD25high T cells, CD14+ monocytes, and plasma for the progression of HIV infection.

BACKGROUND: B7-H3 is an important immune checkpoint molecule that plays a negative role in immune regulation. This study was aimed to explore B7-H3 expression in HIV-infected patients and its clinical significance. METHODS: To explore the expression and clinical significance of B7-H3 in HIV-infected patients, we investigated the B7-H3 expression pattern and the correlation of B7-H3 expression with clinical parameters of HIV-infected patients with different levels of CD4+ T cells. To assess the role of B7-H3 in regulating the function of T cells in HIV infection, we performed a proliferation assay and T cell function test in vitro. RESULTS: B7-H3 expression in HIV-infected patients was significantly higher than that in healthy controls. mB7-H3 expression on CD4+CD25high T cells and CD14+ monocytes increased with disease progression. mB7-H3 expression on CD4+CD25high T cells and monocytes was negatively correlated with lymphocyte count, CD4+T cell count, and positively correlated with HIV viral load in HIV-infected patients. when the number of CD4+ T cells in HIV-infected patients was ≥ 200/µL, sB7-H3 and mB7-H3 expression levels on CD4+CD25high T cells and monocytes were negatively correlated with lymphocyte count, CD4+T cell count. sB7-H3 and mB7-H3 expression on monocytes were positively correlated with HIV viral load. B7-H3 inhibited the proliferation of lymphocytes and the secretion of IFN-γ in vitro, especially the ability of CD8+ T cells to secrete IFN-γ. CONCLUSIONS: B7-H3 played an important negative regulatory role in anti-HIV infection immunity. It could be used as a potential biomarker for the progression of HIV infection and a novel target for the treatment of HIV infection.

Surgery-related characteristics, efficacy, safety and surgical team satisfaction of three-dimensional heads-up system versus traditional microscopic equipment for various vitreoretinal diseases.

PURPOSE: To compare the three-dimensional (3D) heads-up surgery with the traditional microscopic (TM) surgery for various vitreoretinal diseases. METHODS: A medical record review of patients that underwent 3D heads-up or TM vitreoretinal surgeries was performed from May 2020 to October 2021 in this retrospective case-control study. Main outcome measures included surgery-related characteristics, efficacy, safety, and satisfaction feedback from the surgical team. RESULTS: A total of 220 (47.6%) and 242 (52.4%) eyes were included in the 3D and TM groups, respectively. The 3D heads-up system significantly benefits delicate surgical steps, like the epiretinal membrane (ERM) peeling for ERM and internal limiting membrane peeling for idiopathic macular holes (P < 0.05). The 3D heads-up system could facilitate a significantly better visual outcome for pathologic myopic foveoschisis (P = 0.049), while no difference by TM surgery (P = 0.45). For the satisfaction feedback, the 3D heads-up system was rated significantly higher in most subscales and the overall score (P < 0.05). The surgeons' ratings on operating accuracy and the first assistants' rating on operating accuracy and operation cooperation were significantly higher in the TM group than in the 3D group (P < 0.05). Besides that, the 3D heads-up surgery was comparable with TM surgery in the surgery-related characteristics, choice of tamponades, postoperative VA, primary anatomic success, and perioperative complications (P > 0.05). CONCLUSION: The efficacy and safety of the 3D heads-up surgery were generally comparable to the TM surgery. The 3D heads-up system could significantly benefit delicate surgical steps and achieve better surgical team satisfaction.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

[Metabolomic study on urine of chronic inflammation rats treated with Buyang Huanwu Decoction based on UPLC-Q-TOF-MS].

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 µg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

Research progress of BK virus and systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients are often infected by viruses due to deficient immunity or immunosuppressant use. BK virus (BKV)mainly affects the kidney and can also cause multiple organ involvement throughout the body, which is similar to SLE. BKV is mostly a latent infection in vivo. The incidence of virus reactivation is higher in SLE patients. Reactivation of BKV can induce the production of autoantibodies, thereby promoting the occurrence and development of SLE.Purpose: Aim of this article is to review the prevalence and pathegenesis of BKV infection in SLE patients.Method: The literature search was conducted using four different databases including PubMed, Cochrane Library, Scopus and Web of Science.Results: BK virus is higher infection and reactivation in SLE patients. The "hapten carrier" mechanism may lead to the production of autoantibodies. Some immunosuppressive drugs, like leflumide and hydroxychloroquine, may show a protective effect.Conclusions: BKV infection plays a role in the occurrence and development of SLE, and its significance deserves further exploration.

Optical determination of layered-materials InSe thickness via RGB contrast method and regression analysis.

Indium selenide (InSe) features intriguing thickness-dependent optoelectronic properties, and a simple, and precise way to identify the thickness is essential for the rapid development of InSe research. Here, a red, green, and blue (RGB) color contrast method with regression analysis for quantitative correlation of three optical contrasts from RGB channels with the InSe thickness (1-35 nm), is demonstrated. The lower accuracy of the thickness identification obtained from the individual channels was discussed. Moreover, the effective refractive indices in the three RGB regions can be extracted from the Fresnel equation and numerical analysis by finding the best fit to the experimental optical contrast. After further consideration of the wavelength-dependent refractive indices, the slope of the regression line between the estimated thickness and that obtained from the atomic force microscope was improved from 1.59 ± 0.05 to 0.97 ± 0.02. The complex refractive index spectra of InSe (1-10 layers) generated fromab initionumerical calculation results were also adopted to identify the InSe thickness. Compared to dispersion, the evolution of the band structure had less effect on thickness identification. This work could be extended to other layered materials, facilitate the thickness-dependent study of layered materials, and expedite the realization of their practical applications.

Expressions of melanopsins in telencephalon imply their function in synchronizing semilunar spawning rhythm in the mudskipper Boleophthalmus pectinirostris.

The mudskipper Boleophthalmus pectinirostris inhabits intertidal mudflats, exhibiting semilunar reproductive rhythms. To investigate whether melanopsin is possibly involved in the synchronization of the semilunar spawning rhythm in the female mudskipper, we first cloned all four melanopsin subtypes (opn4m1, opn4m3, opn4x1, opn4x2) in B. pectinirostris. Results from RTq-PCR showed that significantly higher transcription levels of all four melanopsin subtypes were observed in the eyes rather than other tissues. In brain, all four melanopsin subtypes were also detectable in different regions, including the telencephalon, in which the expression of melanopsin has not been reported in other teleosts. The transcription levels of opn4m3 and opn4x1 in the telencephalon exhibited a daily fluctuation pattern. When females entered the spawning season, opn4m1 and opn4x1 transcript levels increased significantly in the telencephalon. During the spawning season, the transcript levels of opn4m3 and opn4x1 in the telencephalon appeared to have a cyclic pattern associated with semilunar periodicity, exhibiting two cycles with a peak around the first or the last lunar quarters. Results from ISH showed that, opn4x1 mRNA was localized in the medial of dorsal telencephalic area, dorsal nucleus of ventral telencephalic area (Vd), ventral nucleus of ventral telencephalic area (Vv), anterior part of parvocellular preoptic nucleus, magnocellular part of the magnocellular preoptic nucleus (PMmc), habenular and ventral zone of hypothalamus. Intriguingly, gnrh3 mRNA was also located in Vd, Vv and PMmc. Taken together, our results suggested that melanopsins, e.g. opn4x1, expressed in the telencephalon might mediate semilunar spawning activity in the female mudskipper.

Clinical characteristics of retinal arterial macroaneurysms and prognosis of different interventions.

PURPOSE: To estimate the clinical characteristics of retinal arterial macroaneurysms (RAM) and evaluate the prognosis of different interventions. METHODS: This study is a meta-analysis. The databases PubMed, EMBASE, and Ovid from inception to January 2021 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated by means of Freeman-Tukey variant of arcsine square transformation. RESULTS: Sixty-nine studies involving 1332 patients were finally included. The pooling results indicated that 91% (95% CI [88 ~ 94%]) of the RAM patients were over sixty, 73% (95% CI [68 ~ 77%]) were female, and 73% (95% CI [66 ~ 79%]) have hypertension. By observation, the RAM closure rate was 64% (95% CI [39 ~ 86%]), the visual acuity (VA) improved in 55% (95% CI [40 ~ 71%]) of the patients, and the VA of 64% (95% CI [54 ~ 74%]) hemorrhagic versus 27% (95% CI [15 ~ 41%]) exudative patients improved significantly. By laser, the closure rate was 96% (95% CI [87 ~ 100%]), the VA improved in 73% (95% CI [65 ~ 80%]) of the patients, and the VA of 66% (95% CI [47 ~ 84%]) hemorrhagic versus 35% (95% CI [23 ~ 47%]) exudative patients improved significantly. By anti-VEGF, the closure rate was 98% (95% CI [93 ~ 100%]), the VA improved in 90% (95% CI [74 ~ 100%]) of the patients, and the VA of 58% (95% CI [18 ~ 94%]) hemorrhagic versus 67% (95% CI [31 ~ 96%]) exudative patients improved significantly. CONCLUSION: RAM are most commonly seen in the elderly with a marked female predominance and a strong association with hypertension. Patients receiving laser or anti-VEGF treatments get higher closure rate and better visual prognosis than those with observation alone. Hemorrhagic RAM have a better visual prognosis by observation or laser treatment, while exudative RAM have a better visual prognosis by anti-VEGF treatment.

CLINICAL CHARACTERISTICS OF EALES DISEASE AND THE EFFICACY OF DIFFERENT INTERVENTIONS FOR NEOVASCULAR COMPLICATIONS.

PURPOSE: To evaluate clinical features and manifestations of Eales disease and the efficacy of different interventions. METHODS: The databases PubMed, EMBASE, and Ovid from inception until February 2021 were searched. Pooled analyses included 1) presenting features, 2) symptoms and signs, and 3) postoperative vision outcomes and complications. Statistical analyses were conducted with R software version 3.6.3. RESULTS: Forty-seven studies involving 3,557 patients and 4,959 eyes were included. The pooling results showed that Eales disease was male dominated (94%), bilateral involvement (64%), and mainly occurred in adolescents. Approximately 83% of patients were positive in Mantoux test, and 31% of patients have vitreous tap polymerase chain reaction positive for tuberculosis genome. More than half of the patients had decreased vision at the first clinic visit. The common signs of Eales disease included sclerotic vessels (83%), neovascularization of retina elsewhere (64%) and periphlebitis (51%). Macular changes could be detected in 24% of patients. The most common complication was vitreous hemorrhage, followed by cataracts and retinal detachment. Photocoagulation was directed at nonperfusion or neovascularization areas, with a decrease in the incidence of later pars plana vitrectomy (19%). Anti-vascular endothelial growth factor treatment was suggested for vitreous hemorrhage, which could achieve high visual acuity improvement rate (82%) while increasing the possibility of retinal detachment (18%). Pars plana vitrectomy was indicated in cases with persistent vitreous hemorrhage or retinal detachment, with 56% of patients obtaining visual improvement. Still, 17% of patients needed a second pars plana vitrectomy, mainly because of recurrent vitreous hemorrhage or retinal detachment. CONCLUSION: Eales disease most commonly affects young men. It has diverse clinical features, and management should be based on the progression of the disease.

PUMCH experience and strategy for the management of idiopathic macular hole: a retrospective cohort study.

PURPOSE: To introduce and evaluate a modified therapeutic strategy for idiopathic macular holes (IMH). METHODS: A retrospective review of patients with diagnosis of IMH from July 2016 to January 2020 at Peking Union Medical College Hospital. These patients were managed strictly according to our therapeutic strategy. Their comprehensive clinical data were collected and analyzed. RESULTS: 209 eyes suffering stage II to IV IMH were identified. For stage II IMH, the spontaneous closure rate was 8.9%, the initial success rate of intravitreal injections (IVI) of expansile gas and pars plana vitrectomy (PPV) + internal limiting membrane peeling (ILMP) + air tamponade was 84.2% and 100%, respectively. The initial success rate of PPV + ILMP + air tamponade for stage III and stage IV IMH was 89.8% and 86.4%, respectively. Following our intervention strategy, stage II IMH achieved a final IMH closure rate of 100%, stage III of 99% and stage IV of 97%. The final best corrected visual acuity was significantly improved (P < 0.05). Sitting position air-fluid (A-F) exchange alone successfully induced IMH closure in 7/19 eyes that did not achieve IMH closure by initial PPV. For three refractory cases that failed additional PPV + ILM stuffing, intraoperative OCT assisted PPV + sub-retinal BSS injection successfully induced the IMH closure. As the remaining three unclosed IMH cases were dry and stable, no more interventions were conducted. CONCLUSION: The general IMH closure rate based on our therapeutic strategy was satisfactory with a favorable prognosis. IVI expansile gas and sitting position A-F exchange were effective and highly cost-effective under certain circumstances.

Enantioselective Synthesis of Axially Chiral Biaryls by Diels-Alder/Retro-Diels-Alder Reaction of 2-Pyrones with Alkynes.

The enantioselective synthesis of axially chiral biaryls by a copper-catalyzed Diels-Alder/retro-Diels-Alder reaction of 2-pyrones with alkynes is reported herein. Using electron-deficient 2-pyrones and electron-rich 1-naphthyl acetylenes as the reaction partners, a broad range of axially chiral biaryl esters are obtained in excellent yields (up to 97% yield) and enantioselectivities (up to >99% ee). DFT calculations reveal the reaction mechanism and provide insights into the origins of the stereoselectivities. The practicality and robustness of this reaction are showcased by gram-scale synthesis. The synthetic utilizations are demonstrated by the amenable transformations of the products.