How to identify juxtaglomerular cell tumor by ultrasound: a case series and review of the literature.

PURPOSE: To study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT). METHODS: From January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively. RESULTS: The 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9-5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm. CONCLUSIONS: JGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.

The effects on pain, physical function, and quality of life of quadriceps strengthening exercises combined with Baduanjin qigong in older adults with knee osteoarthritis: a quasi-experimental study.

BACKGROUND: Exercise is recommended as a principal treatment for individuals with knee osteoarthritis (KOA). However, the best choice for an optimal exercise program able to promote long-term compliance in KOA patients is not clear. This study aims to compare the effect of combined exercise (CE: quadriceps strengthening exercises (QSE) and Baduanjin qigong training (BDJ)) versus QSE alone and BDJ alone on older adults with KOA. METHODS: A three-arm, quasi-experimental trial with repeated measurements was used. As a cluster randomized trial, participants from three community centers were assigned respectively to QSE group, BDJ group and CE group. We assessed pain intensity, physical function, self-efficacy, and health-related quality-of-life (HRQoL) using standardized instruments at baseline, 3 months and 6 months follow-up. RESULTS: One hundred and twenty-eight participants with KOA aged over 60 completed the study. Over the 6 months, there were significant group interaction effects on pain intensity (F = 28.888, P < 0.001), physical function (F = 26.646, P < 0.001), and self-efficacy (F = 22.359, P < 0.001), and, based on a short form-12 item health survey questionnaire (SF-12), physical component summary (F = 7.470, P < 0.001), and mental component summary (F = 10.207, P < 0.001). Overall, the CE group exhibited significantly greater improvement in all outcomes when compared to the QSE group and the BDJ group. CONCLUSIONS: CE treatment is more effective than QSE and BDJ in pain relief, increasing physical function, improving self-efficacy, and raising quality-of-life in community-dwelling KOA older adults. Moreover, it promotes long-term compliance in KOA community patients. TRIAL REGISTRATION: Chinese Clinical Trails Registry number ChiCTR2000033387 (retrospectively registered). Registered 30 May 2020.

The comparison of the effects of local cooling and heating on apoptosis and pyroptosis of early-stage pressure ulcers in rats.

The exploration of an effective method for preventing and treating pressure ulcers (PUs) is a hot topic in medical research. Recently, disputes about the choice of heat and cold therapies have emerged for the prevention and treatment of clinical PUs. The present study was designed to compare the effect of cool and heat therapies on pyroptosis and apoptosis of early-stage PUs in rats. Sixty SD rats of SPF grade were randomly divided into the sham group, model group, heating group, and cooling group. We established a rat model of early-stage PUs by using an ischemia-reperfusion method. At the end of the experiment, the tissue underneath the compressed region was collected for hematoxylin and eosin staining, transmission electron microscopy, immunohistochemistry, immunofluorescence staining, a TdT-mediated dUTP nick-end labeling assay, a Western blot analysis, and a mitochondrial swelling experiment. Our results suggested that the mitochondrial apoptotic pathway and pyroptosis were involved in the formation of early-stage PUs, and local heating increased the PU injury in rats, while local cooling reduced the PU injury in rats. This study showed that heat therapy might not be suitable for the clinical treatment and care of early-stage PUs, while cold therapy may be more appropriate.

Effects of a nurse-led transitional care programme on readmission, self-efficacy to implement health-promoting behaviours, functional status and life quality among Chinese patients with coronary artery disease: A randomised controlled trial.

AIMS AND OBJECTIVES: To examine the effectiveness of a nurse-led transitional care programme on readmission, self-efficacy to implement health-promoting behaviours, functional status and life quality among Chinese patients with coronary artery disease. BACKGROUND: Coronary artery disease is a major cause of mortality in China. Transitional care could help to ensure improved patient outcomes. Nevertheless, our knowledge of how to perform transitional care for patients with coronary artery disease is insufficient in mainland China. DESIGN: Randomised controlled trial. METHODS: The nurse-led transitional care intervention in the experimental group adopted the Omaha system and Pender's health-promoting model as its frameworks. The control group received a comparable length routine care and follow-up contacts. Evaluations were conducted at baseline before discharge and after 7 months after discharge using hospital readmission rate, self-rated abilities for health practices scale and Seattle Angina Questionnaire for functional status and life quality. Data were collected between March 2014-October 2014. RESULTS: Compared with the control group, participants in the experimental group showed greater self-efficacy to implement health-promoting behaviours, more angina stability, less angina frequency, more satisfaction with treatment and better quality of life. The difference in readmission rate and physical limitations was not significant between the two groups. CONCLUSION: This study provides evidence for the effectiveness of a nurse-led transitional care programme in improving the ability to implement health-promoting behaviours, the functional status and life quality among Chinese patients with coronary artery disease. RELEVANCE TO CLINICAL PRACTICE: The nurse-led transitional care programme is helpful for coronary artery disease patients to promote their effective transfer from hospital to community and provide an evidence for nursing managers to train their nurses for transitional care knowledge and skills.

[Analysis of influence of inflammatory factor in patients with ovarian endometriosis follicular fluid on the outcome of in vitro fertilization].

OBJECTIVE: To observe the effect of follicular fluid IL-6, TNF-α on the clinical outcome of in vitro fertilization and embryo transfer (IVF-ET) in patients with ovarian endometriosis. METHOD: From June 2013 to June 2014, the data of 64 (from Tangshan Maternal and Child Health Hospital IVF center) ovarian endometriosis patients was analyzed retrospectively. 58 infertility cases caused by male side were used as control group. Oocyte retrieval rate, M II oocytes rate, fertilization rate, recovery-intracytoplasmic sperm injection (R-ICSI) rate, good quality embryo rate, biochemical pregnancy rate and clinical pregnancy rate were analyzed and compared between two groups. Changes in the expression of follicular fluid IL-6, TNF-α were detected. RESULTS: Oocyte retrieval rate, M II oocytes rate, fertilization rate, good quality embryo rate, biochemical pregnancy rate and clinical pregnancy rate in ovarian endometriosis group were significantly lower than those in the control group (all P < 0.05), while R-ICSI rate increased in ovarian endometriosis group compared with control group (P < 0.05). IL-6, TNF-α expressions of follicular fluid were higher in affected side of ovarian endometriosis patients than those in the unaffected side and those in control group. CONCLUSION: Inflammation microenvironment of the follicular fluid may influence IVF-ET outcomes in ovarian endometriosis patients.

Liver myofibroblasts from hepatitis B related liver failure patients may regulate natural killer cell function via PGE2.

BACKGROUND: Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury. However, few studies have investigated the phenotypes and functions of NK cells involved in hepatitis B related liver failure (LF), and the precise mechanism underlying NK cell regulation is not fully understood. METHODS: We detected the percentage and function of peripheral NK cells both in hepatitis B related LF patients and healthy volunteers by flow cytometry and isolated the liver myofibroblasts (LMFs) from hepatitis B related LF livers. To determine the possible effects of LMFs on NK cells, mixed cell cultures were established in vitro. RESULTS: We found a down-regulated percentage of peripheral NK cells in hepatitis B related LF patients, and their NK cells also displayed decreased activated natural cytotoxicity receptors (NCRs) and cytokine production. In a co-culture model, LMFs sharply attenuated IL-2-induced NK cell triggering receptors, cytotoxicity, and cytokine production. The inhibitory effect of LMFs on NK cells correlated with their ability to produce prostaglandin (PG) E2. CONCLUSION: These data suggest that LMFs may protect against immune-mediated liver injury in hepatitis B related LF patients by inhibiting NK cell function via PGE2.

Liver myofibroblasts up-regulate monocyte CD163 expression via PGE2 during hepatitis B induced liver failure.

BACKGROUND: Although patients with liver failure exhibit a generalized inflammatory-imbalance status, substantial evidence indicates that this immunosuppressive or anti-inflammatory state may be deleterious. Increased expression of CD163 (known to be involved in several anti-inflammatory functions of the immune system) in patients with liver failure is significantly correlated with a fatal outcome. However, little is known of the regulatory mechanisms that influence the expression of CD163. METHODS: We assessed the expression of CD163 on monocytes from both circulating cells and the liver tissues of patients with hepatitis B induced liver failure using flow cytometry and isolated the myofibroblasts from diseased livers. The ability of human liver myofibroblasts to regulate CD163 expression on monocytes was studied in vitro. RESULTS: We showed that CD163⁺ monocytes were enriched primarily in diseased livers and that they were associated with liver myofibroblasts in the same area. Accordingly, liver myofibroblasts were significantly superior to normal skin fibroblasts in inducing the expression of CD163 on monocytes in vitro. Moreover, we found that liver myofibroblasts triggered the activation of monocytes by secreting PGE2. Inhibition of PGE2 production in liver myofibroblasts using NS-398 markedly reduced CD163 expression in vitro. CONCLUSION: These results suggest that liver myofibroblasts play a direct role in regulating the expression of CD163 on monocytes in human liver tissues and thereby may regulate monocyte function during hepatitis B induced liver failure.

Electronic transport through a benzene-shaped quantum dots system.

Based on the nonequilibrium Green function method, quantum transport through a benzene-shaped quantum dots system is studied. It is shown that the conductance spectrum is sensitive to the arrangement of energy levels of dots. When the energy levels of dots are mismatched, the conductance shows apparent asymmetric structure and striking novel conductance dips appear due to the interference between two distinct paths. The differential conductance as a function of magnetic flux always exhibits 2pi period. An overall suppression of differential conductance emerges for the condition that the levels of dots are all aligned and phi = (2n + 1)pi (n is an integer). In addition, the influence of temperature on the differential conductance is presented.

A Dual Triggering Scheme to Adaptive Fuzzy Resilient Control of Switched Nonlinear Systems Against Mixed Attacks.

A dual event-triggered adaptive fuzzy resilient control scheme for a class of switched nonlinear systems with vanishing control gains under mixed attacks is proposed in this article. The scheme proposed achieves dual triggering in the channels of sensor-to-controller and controller-to-actuator by designing two new switching dynamic event-triggering mechanisms (ETMs). An adjustable positive lower bound of interevent times for each ETM is found to preclude Zeno behavior. Meanwhile, mixed attacks, that is, deception attacks on sampled state and controller data and dual random denial-of-service attacks on sampled switching signal data, are handled by constructing event-triggered adaptive fuzzy resilient controllers of subsystems. Compared with the existing works for switched systems with only single triggering, more complex asynchronous switching caused by dual triggering and mixed attacks and subsystem switching is addressed. Further, the obstacle caused by vanishing control gains at some points is eliminated by proposing an event-triggered state-dependent switching law and introducing vanishing control gains into a switching dynamic ETM. Finally, a mass-spring-damper system and a switched RLC circuit system are applied to verify the obtained result.

Global Event-Triggered Funnel Control of Switched Nonlinear Systems via Switching Multiple Lyapunov Functions.

In this article, the global event-triggered (ET) funnel tracking control problem is studied for a class of switched nonlinear systems with structural uncertainties, where the solvability of the control problem for each subsystem is not needed. A switching multiple Lyapunov functions (MLFs) method is established, where MLFs are designed to handle switched inverse dynamics, and a switching barrier Lyapunov function is constructed to address switched sampled errors that may compromise system stability. This is achieved alongside a new switching dynamic event-triggering mechanism (DETM). By combining this method with backstepping, a dwell-time state-dependent switching law and an ET funnel controller of each subsystem are constructed, effectively eliminating the issue of the "explosion of complexity" encountered in traditional backstepping without using dynamic surface control or command filters. Additionally, the designed switching DETM ensures that the tracking error always evolves within a performance funnel in any consecutive triggering interval, excluding Zeno behavior, and guaranteeing positive constant lower bounds for two consecutive triggering intervals and any switching interval, respectively. Finally, an example is provided to show the validity of the theoretical results.

From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.

Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy's effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy.

Floral Response to Heat: A Study of Color and Biochemical Adaptations in Purple Chrysanthemums.

Chrysanthemums are among the world's most popular cut flowers, with their color being a key ornamental feature. The formation of these colors can be influenced by high temperatures. However, the regulatory mechanisms that control the fading of chrysanthemum flower color under high-temperature stress remain unclear. This study investigates the impact of high temperatures on the color and biochemical responses of purple chrysanthemums. Four purple chrysanthemum varieties were exposed to both normal and elevated temperature conditions. High-temperature stress elicited distinct responses among the purple chrysanthemum varieties. 'Zi Feng Che' and 'Chrystal Regal' maintained color stability, whereas 'Zi Hong Tuo Gui' and 'Zi lian' exhibited significant color fading, particularly during early bloom stages. This fading was associated with decreased enzymatic activities, specifically of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), indicating a critical period of color development under heat stress. Additionally, the color fading of 'Zi Lian' was closely related to the increased activity of the peroxidase (POD) and polyphenol oxidase (PPO). Conversely, a reduction in ß-glucosidase (ßG) activity may contribute significantly to the color steadfastness of 'Zi Feng Che'. The genes Cse_sc027584.1_g010.1 (PPO) and Cse_sc031727.1_g010.1 (POD) might contribute to the degradation of anthocyanins in the petals of 'Zi Hong Tuo Gui' and 'Zi Lian' under high-temperature conditions, while simultaneously maintaining the stability of anthocyanins in 'Zi Feng Che' and 'Chrystal Regal' at the early bloom floral stage. The findings of this research provide new insights into the physiological and biochemical mechanisms by which chrysanthemum flower color responds to high-temperature stress.

Cell-specific localization of ß-synuclein in the mouse retina.

ß-synuclein, a member of the synuclein family, is frequently co-expressed with α-synuclein in the neural system, where it serves to inhibit abnormal aggregation of α-synuclein in neurodegenerative diseases. Beyond its role in pathological conditions, ß-synuclein plays various functions independently of α-synuclein. In our investigation, we discovered a broader expression of ß-synuclein in the mouse retina compared to α-synuclein. This widespread pattern implies its potential significance in the retina. Through detailed examination via light- and electron-microscopic immunocytochemistry, we identified ß-synuclein expression from the inner segment (IS) and outer segment (OS) of photoreceptor cells to the ganglion cell layer (GCL). Our findings unveiled unique features, including ß-synuclein immunoreactive IS and OS of cones, higher expression in cone pedicles than in rod spherules, absence in horizontal cells, limited expression in cone bipolar dendrites and somas, higher expression in cone bipolar terminals, presence in most amacrine cells, and expression in almost majority of somas in GCL with an absence in intrinsically photosensitive retinal ganglion cell (ipRGCs) processes. Notably, all cholinergic amacrine cells express high ß- but not α-synuclein, while dopaminergic amacrine cells express α-synuclein exclusively. These distinctive expression patterns offer valuable insights for further exploration into the functions of ß-synuclein and its potential role in synuclein pathology within the retina.

Dynamic Event-Triggered Adaptive NN Control for Switched Uncertain Nonlinear Systems.

This article is concerned with the problem of dynamic event-triggered adaptive neural network (NN) control for a class of switched strict-feedback uncertainty nonlinear systems. A novel switched command filter-based dynamic event-triggered adaptive NN control approach is set up by exploiting the backstepping and command filter and the common Lyapunov function method. Since adaptive controllers of subsystems are event triggered, then if the switching happens between any two consecutive triggering instants, asynchronous switching will arise between candidate controllers of subsystems and subsystems. Unlike the existing literature, where maximum asynchronous time is restricted, without any strict limitations on maximum asynchronous time being needed in this article, the asynchronous switching problem is directly handled by proposing a novel switching dynamic event-triggered mechanism (DETM) and event-triggered adaptive controllers of subsystems. Moreover, a piecewise constant variable is introduced into the switching DETM, which overcomes the difficulty of switched measurement error being discontinuous. Also, a strictly positive lower bound of interevent times is obtained. Finally, a continuous stirred tank reactor system and a numerical example are presented to demonstrate the effectiveness of the developed approach.

Influencing factors of sarcopenia in older adults based on the Newman system model: a case-control study.

PURPOSE: Research on sarcopenia has primarily focused on single fields such as physiology or psychology. However, there is a lack of clear evidence to determine the influence of social factors on sarcopenia. Therefore, our aim was to explore the multidimensional factors that contribute to sarcopenia in older adults within the community. METHODS: In this retrospective case-control study, we applied the diagnostic criteria from The Asian Working Group on Sarcopenia (AWGS) 2019 to categorize study subjects into control and case groups. Our aim was to examine the impact of physical, psychological, and social factors on community-dwelling older adults with sarcopenia across multiple dimensions. We utilized descriptive statistics, as well as simple and multivariate logistic regression analyses, to analyze the data. We compared the odds ratios (OR) of the factors between the two groups and ranked the importance of the influencing factors using the XGBoost algorithm in Python software. RESULTS: Combined with multivariate analysis and XGBoost algorithm results, it can be seen that physical activity is the strongest predictor of sarcopenia [OR] = 0.922(95% CI 0.906-0.948), followed diabetes mellitus [OR] = 3.454(95% CI 1.007-11.854), older age [OR] = 1.112(95% CI 1.023-1.210), divorced or widowed [OR] = 19.148 (95% CI 4.233-86.607), malnutrition [OR] = 18.332(95% CI 5.500-61.099), and depressed [OR] = 7.037(95% CI 2.391-20.710). CONCLUSIONS: Factors associated with the development of sarcopenia in community-dwelling older adults cover a multiplicity of physical, psychological, and social factors, physical activity, diabetes mellitus, age, marital status, nutrition, and depression were important factors that have an impact on sarcopenia. REGISTRATION NUMBER: ChiCTR2200056297.

Distribution and synaptic organization of substance P-like immunoreactive neurons in the mouse retina.

Substance P (SP), a neuroprotective peptidergic neurotransmitter, is known to have immunoreactivity (IR) localized to amacrine and/or ganglion cells in a variety of species' retinas, but it has not yet been studied in the mouse retina. Thus, we investigated the distribution and synaptic organization of SP-IR by confocal and electron microscopy immunocytochemistry in the mouse retina. SP-IR was distributed in the inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Most of the SP-IR somas belonged to amacrine cells (2.5% of all) in the INL and their processes stratified into the S1, S3, and S5 layers of the IPL, with the most intense band in the S5 layer. Some SP-IR somas can also be observed in the GCL, which were identified as displaced amacrine cells (82%, 1269/1550) and ganglion cells (18%, 281/1550) by antibodies against AP2α and RBPMS, respectively. Such SP-IR ganglion cells (1.2% of all RGCs) can be further divided into 3 subgroups expressing SP/α-Synuclein (α-Syn), SP/GAD67, and/or SP/GAD67/α-Syn. Possible physiological and pathological roles of these ganglion cells are discussed. Further, electron microscopy evidence demonstrates that SP-IR amacrine cells receive major inputs from other SP-IR amacrine cell processes (146/242 inputs) and output mostly to SP-negative amacrine cell processes (291/673 outputs), suggesting series inhibition among amacrine cells. These results reveal for the first time an explicit distribution, novel ganglion cell features, and synaptic organization of SP-IR in the mouse retina, which is important for the future use of mouse models to study the roles of SP in healthy and diseased (including Parkinson's disease) retinal states.

[Distribution of monocyte subsets and their surface CD31 intensity are associated with disease course and severity of hemorrhagic fever with renal syndrome].

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14++CD16-), intermediated monocyte subsets (CD14++CD16+) and non-classical monocyte subsets (CD14+CD16++) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.

Expression of α-Synuclein in the mouse retina is confined to inhibitory presynaptic elements.

α-Synuclein (α-Syn) is enriched in presynaptic terminals of the central nervous system including the retina and plays a role in the synaptic vesicle cycle and synaptic transmission. Abnormal aggregation of α-Syn is considered to be the main component of the Lewy bodies that are the pathological hallmarks of Parkinson's disease. Although expression pattern of α-Syn has been described in the retinas, its precise cellular and subcellular locations are poorly understood. We investigated the precise expression of α-Syn using light microscopy (LM) and electron microscopy (EM) with antibodies against α-Syn in the mouse retina. We found that the majority of α-Syn immunoreactivity (IR) is located in GABAergic, glycinergic, and dopaminergic amacrine cells, and their processes often make a direct synapse to other labeled or unlabeled amacrine profiles, bipolar cell terminals, or ganglion cell dendrites. Further, our LM and immuno-EM results confirm the absence of α-Syn in excitatory photoreceptors, bipolar cell bodies, and their ribbon synapses, providing evidence, for the first time, that ribbon synapses do not express α-Syn. Additionally, α-Syn IR is located in the ganglion cells, some of which are intrinsically photosensitive retinal ganglion cells. These results reveal a previously unappreciated inhibitory synapse-specific expression pattern of α-Syn in the retina, suggesting that α-Syn may play a distinct role in the modulation and integration of inhibitory synaptic transmission in the retina.

Rod bipolar cells receive cone photoreceptor inputs through both invaginating synapses and flat contacts in the mouse and guinea pig retinas.

The light pathways are segregated into rod and cone pathways in which rods synapse with rod bipolar cells (RBCs), while cones contact cone bipolar cells (CBCs). However, previous studies found that cones can make synapse with RBCs (cone-RBC synapses) and rods can contact OFF CBC in primate and rabbit retinas. Recently, such cone-RBC synapses have been reported physiologically and morphologically in the mouse retina. Nevertheless, the precise subcellular evidence to determine whether it is the invaginating synapse or the flat contact remains absent. This is due to a lack of immunochemically verified ultrastructural data. Here, we investigated the precise expression of protein kinase C alpha (PKCα) using pre-embedding immunoelectron microscopy (immuno-EM) with a monoclonal antibody against PKCα, a biomarker for the RBCs. We determined the nanoscale localization of PKCα in the outer plexiform layer of the mouse and guinea pig retinas. Our results demonstrate the existence of both the direct invaginating synapse and the basal/flat contact of the cone-RBCs, providing for the first time immunochemically verified ultrastructural evidence for the cone-RBC synapse in the mouse and guinea pig retinas. These results suggest that the cross talk between cone and rod pathways is much more extensive than previously assumed.

Identification of Single-Nucleotide Polymorphisms (SNPs) Associated with Heat Tolerance at the Reproductive Stage in Synthetic Hexaploid Wheats Using GWAS.

The projected rise in global ambient temperature by 3-5 °C by the end of this century, along with unpredicted heat waves during critical crop growth stages, can drastically reduce grain yield and will pose a great food security challenge. It is therefore important to identify wheat genetic resources able to withstand high temperatures, discover genes underpinning resilience to higher temperatures, and deploy such genetic resources in wheat breeding to develop heat-tolerant cultivars. In this study, 180 accessions of synthetic hexaploid wheats (SHWs) were evaluated under normal and late wheat growing seasons (to expose them to higher temperatures) at three locations (Islamabad, Bahawalpur, and Tando Jam), and data were collected on 11 morphological and yield-related traits. The diversity panel was genotyped with a 50 K SNP array to conduct genome-wide association studies (GWASs) for heat tolerance in SHW. A known heat-tolerance locus, TaHST1, was profiled to identify different haplotypes of this locus in SHWs and their association with grain yield and related traits in SHWs. There was a 36% decrease in grain yield (GY), a 23% decrease in thousand-grain weight (TKW), and an 18% decrease in grains per spike (GpS) across three locations in the population due to the heat stress conditions. GWASs identified 143 quantitative trait nucleotides (QTNs) distributed over all 21 chromosomes in the SHWs. Out of these, 52 QTNs were associated with morphological and yield-related traits under heat stress, while 15 of them were pleiotropically associated with multiple traits. The heat shock protein (HSP) framework of the wheat genome was then aligned with the QTNs identified in this study. Seventeen QTNs were in proximity to HSPs on chr2B, chr3D, chr5A, chr5B, chr6D, and chr7D. It is likely that QTNs on the D genome and those in proximity to HSPs may carry novel alleles for heat-tolerance genes. The analysis of TaHST1 indicated that 15 haplotypes were present in the SHWs for this locus, while hap1 showed the highest frequency of 25% (33 SHWs). These haplotypes were significantly associated with yield-related traits in the SHWs. New alleles associated with yield-related traits in SHWs could be an excellent reservoir for breeding deployment.