Multiple Calcium Channel Types with Unique Expression Patterns Mediate Retinal Signaling at Bipolar Cell Ribbon Synapses.

Retinal bipolar cells (BCs) compose the canonical vertical excitatory pathway that conveys photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca2+ influx through voltage-gated Ca2+ (CaV) channels mediating L-type currents, the molecular identity of CaV channels in BCs is uncertain. Therefore, we combined molecular and functional analyses to determine the expression profiles of CaV α1, ß, and α2δ subunits in mouse rod bipolar (RB) cells, BCs from which the dynamics of synaptic transmission are relatively well-characterized. We found significant heterogeneity in CaV subunit expression within the RB population from mice of either sex, and significantly, we discovered that transmission from RB synapses was mediated by Ca2+ influx through P/Q-type (CaV2.1) and N-type (CaV2.2) conductances as well as the previously-described L-type (CaV1) and T-type (CaV3) conductances. Furthermore, we found both CaV1.3 and CaV1.4 proteins located near presynaptic ribbon-type active zones in RB axon terminals, indicating that the L-type conductance is mediated by multiple CaV1 subtypes. Similarly, CaV3 α1, ß, and α2δ subunits also appear to obey a "multisubtype" rule, i.e., we observed a combination of multiple subtypes, rather than a single subtype as previously thought, for each CaV subunit in individual cells.SIGNIFICANCE STATEMENT Bipolar cells (BCs) transmit photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca2+ influx through L-type voltage-gated Ca2+ (CaV) channels, the molecular identity of CaV channels in BCs is uncertain. Here, we report unexpectedly high molecular diversity of CaV subunits in BCs. Transmission from rod bipolar (RB) cell synapses can be mediated by Ca2+ influx through P/Q-type (CaV2.1) and N-type (CaV2.2) conductances as well as the previously-described L-type (CaV1) and T-type (CaV3) conductances. Furthermore, CaV1, CaV3, ß, and α2δ subunits appear to obey a "multisubtype" rule, i.e., a combination of multiple subtypes for each subunit in individual cells, rather than a single subtype as previously thought.

Millimeter-wave noise generation based on a monolithically integrated dual-mode chaotic laser.

A millimeter-wave noise generation scheme is proposed in this paper. The scheme is based on a monolithically integrated dual-mode chaotic laser, which consists of a distributed Bragg feedback (DFB) section, a phase section, and an optical amplification section. The output spectrum state of the dual-mode laser can be controlled by adjusting the injection current in the three regions. The monolithically integrated dual-mode chaotic laser has stable chaotic output and can be used as a light source for integrated millimeter-wave noise source. As a feasibility demonstration, a dual-mode chaotic laser with a mode interval of 2.05 nm was generated in the experiment, the optical mixing on a photodetector produced millimeter-wave noise with a center frequency of 259 GHz and a bandwidth of 44 GHz (237-281 GHz), achieving a typical value of excess noise ratio of 47 dB. It has the advantages of high noise source utilization, small noise source volume, and high integration.

An Improved Pig Counting Algorithm Based on YOLOv5 and DeepSORT Model.

Pig counting is an important task in pig sales and breeding supervision. Currently, manual counting is low-efficiency and high-cost and presents challenges in terms of statistical analysis. In response to the difficulties faced in pig part feature detection, the loss of tracking due to rapid movement, and the large counting deviation in pig video tracking and counting research, this paper proposes an improved pig counting algorithm (Mobile Pig Counting Algorithm with YOLOv5xpig and DeepSORTPig (MPC-YD)) based on YOLOv5 + DeepSORT model. The algorithm improves the detection rate of pig body parts by adding two different sizes of SPP networks and using SoftPool instead of MaxPool operations in YOLOv5x. In addition, the algorithm includes a pig reidentification network, a pig-tracking method based on spatial state correction, and a pig counting method based on frame number judgment on the DeepSORT algorithm to improve pig tracking accuracy. Experimental analysis shows that the MPC-YD algorithm achieves an average precision of 99.24% in pig object detection and an accuracy of 85.32% in multitarget pig tracking. In the aisle environment of the slaughterhouse, the MPC-YD algorithm achieves a correlation coefficient (R2) of 98.14% in pig counting from video, and it achieves stable pig counting in a breeding environment. The algorithm has a wide range of application prospects.

Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL-4-producing T cells and regulatory T cells.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune-mediated destruction of insulin-producing ß cells. Recent studies showed that in addition to malaria, artemisinin and its derivative, artesunate (AS), could alleviate several autoimmune diseases. However, whether AS has a role in the prevention or treatment of T1D is still unknown. Therefore, in this study we administrated AS or DMSO in the drinking water of nonobese diabetic (NOD) mice, a mouse model of T1D. We found that AS administration significantly prevented the incidence of T1D. The frequency of IL-4-producing CD4+ single-positive T cells and CD8+ T cells was significantly elevated, and IFN-γ-producing T cells were reduced in the spleen and pancreatic lymph nodes. In the pancreas, the skewing to IL-4-producing T cells was also observed. In addition, more regulatory T cells were found in the pancreas. mRNA levels of proinflammatory cytokines, including TNF-α and IL-6, were decreased. In addition, AS administration promoted the functional maturity of ß cells in vitro. Our findings demonstrate that AS administration can prevent T1D in NOD mice mainly by reducing autoimmune T cells and increasing protective T cells. Our data constitute the first functional study of AS in T1D, which may provide a new rationale for future translational studies.-Li, Z., Shi, X., Liu, J., Shao, F., Huang, G., Zhou, Z., Zheng, P. Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL-4-producing T cells and regulatory T cells.

Facile Synthesis of Ultra-Small Few-Layer Nanostructured MoSe2 Embedded on N, P Co-Doped Bio-Carbon for High-Performance Half/Full Sodium-Ion and Potassium-Ion Batteries.

Sodium/potassium-ion batteries (SIBs/PIBs) arouse intensive interest on account of the natural abundance of sodium/potassium resources, the competitive cost and appropriate redox potential. Nevertheless, the huge challenge for SIBs/PIBs lies in the scarcity of an anode material with high capacity and stable structure, which are capable of accommodating large-size ions during cycling. Furthermore, using sustainable natural biomass to fabricate electrodes for energy storage applications is a hot topic. Herein, an ultra-small few-layer nanostructured MoSe2 embedded on N, P co-doped bio-carbon is reported, which is synthesized by using chlorella as the adsorbent and precursor. As a consequence, the MoSe2 /NP-C-2 composite represents exceedingly impressive electrochemical performance for both sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs). It displays a promising reversible capacity (523 mAh g-1 at 100 mA g-1 after 100 cycles) and impressive long-term cycling performance (192 mAh g-1 at 5 A g-1 even after 1000 cycles) in SIBs, which are some of the best properties of MoSe2 -based anode materials for SIBs to date. To further probe the great potential applications, full SIBs pairing the MoSe2 /NP-C-2 composite anode with a Na3 V2 (PO4 )3 cathode also exhibits a satisfactory capacity of 215 mAh g-1 at 500 mA g-1 after 100 cycles. Moreover, it also delivers a decent reversible capacity of 131 mAh g-1 at 1 A g-1 even after 250 cycles for PIBs.

Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study.

BACKGROUND: Knee osteoarthritis (KOA) is a degenerative joint disease leading to pain and disability for which no curative treatment exists. Intra-articular (IA) therapies are part of this multimodal approach and are approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA). Platelet-rich plasma (PRP), hyaluronic acid (HA), and corticosteroids (CS) have been increasingly used in recent years to treat KOA. PURPOSE: To determine whether IA-PRP was superior to IA-HA or IA-CS administration routes in these patients. MATERIAL AND METHODS: In this trial the patients were randomized to IA-HA (2 ml/week, for 3 weeks), IA-CS (1 ml) or IA-PRP (3 times, 4 ml, every 3 weeks) groups. The outcome was assessed using the Western Ontario and McMaster Universities (WOMAC) score prior to the first injection and then at 3, 6, 9 and 12 months. Pain was evaluated by a visual analogue scale (VAS) prior to treatment and after 12 months. RESULTS: In this study 120 patients were randomized into 3 groups. There was a significant improvement in all scores (WOMAC, VAS) in each group compared to the pretreatment values (P < 0.05). The mean WOMAC scores for the IA-HA group from pretreatment to 3, 6, 9, and 12 months were 47.23 ± 5.37, 25.02 ± 4.98, 26.38 ± 5.20, 27.86 ± 4.34, and 30.64 ± 8.36, respectively. Similar improvements were noted in the IA-CS and IA-PRP groups. There were no significant differences in the WOMAC scores between the 3 groups 3 months after treatment (P > 0.05) but IA-PRP showed significantly lower scores 6, 9 and 12 months after treatment (P < 0.05). CONCLUSION: Intra-articular PRP injections into the knee for symptomatic early stages of KOA are a valid treatment option. The clinical efficacy of IA-PRP is comparable to that of the IA-HA and IA-CS forms after 3 months and the long-term efficacy of IA PRP is superior to IA-HA and IA-CS.

Comparison of the outcomes of cannulated screws vs. modified tension band wiring fixation techniques in the management of mildly displaced patellar fractures.

BACKGROUND: K wire fixation with tension band wiring has conventionally been used for the open reduction and internal fixation of the patella. However, it suffers from distinct disadvantages such as implant irritation, need for open reduction, incidence of palpable implants, and need for subsequent implant removal. A smaller incision with percutaneous fixation may be an alternative to this established conventional technique. Thus, the purpose of this trial was to compare the treatment outcomes of patients with mildly displaced patellar fractures treated with closed reduction and percutaneous cannulated screw fixation (CRCF) as compared to open reduction and tension band wiring fixation (ORTF). Specifically, we aimed to determine whether cannulated screw fixation was associated with improved clinical outcomes at 12 months as measured using the Lysholm score, pain scores, degree of flexion, range of motion, time to radiographic union, radiographic outcomes, and complication rates. METHODS: Sixty-three patients with transverse patellar fractures displaced less than 8 mm were included in this prospective, randomized, controlled trial, with 52 patients in the final data analysis. Thirty-two patients were operatively treated by CRCF with either two or three cannulated screws. Thirty-one patients were operatively treated by conventional ORTF using the modified tension band technique. At postoperative intervals of 3, 6, and 12 months, knee function was evaluated using the Lysholm score, pain was assessed using the visual analog scale (VAS) score, and active knee extensions and flexion were measured in degrees by goniometry. RESULTS: The CRCF group had average Lysholm scores of 84.4 ± 5.8, 86.7 ± 6.4, and 93.2 ± 5.3 after 3, 6, and 12 months, respectively, which were significantly greater than those of the ORTF group (79.0 ± 5.3, p = 0.001; 81.5 ± 4.6, p = 0.002; and 89.8 ± 6.2, p = 0.039, respectively). Lower pain and squatting scores were the main reasons for the poorer Lysholm scores in the ORTF group. The VAS scores showed that the CRCF group had lower pain scores and better flexion and total range of motion (ROM) compared with the ORTF group after 3 and 6 months, although both groups had similar outcomes after 12 months. The mean fracture healing time of 2.65 months was similar in the CRCF groups (2.77 months; p = 0.440). Complication rates were 3/26 (11.5 %) in the CRCF group and 14/26 (53.4 %) in the ORTF group. Two patients in the CRCF group and eight patients in the ORTF group experienced skin irritation. In addition, two (7.7 %) patients in the CRCF group and 11 (42.3 %) patients in the ORTF group required implant removal because of symptoms due to the presence of the implants. CONCLUSION: Surgical treatment of mild displaced (less than 8 mm) transverse patellar fractures by the CRCF technique provides satisfactory clinical results and excellent knee function, with little pain and a low incidence of complications at early follow-up (up to 6 months). These results suggest that the CRCF technique may be a superior alternative to conventional ORTF. Registration Trial (Chinese Clinical Trial Register): Current Controlled Trials ChiCTR-PRCH-14005017, registration dates 2014-06-14.

Comprehensive Characterization of a Subfamily of Ca2+-Binding Proteins in Mouse and Human Retinal Neurons at Single-Cell Resolution.

Ca2+-binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca2+ sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previously hypothesized. Remarkably, mouse rods and human cones exclusively expressed CaBP4, whereas mouse cones and human rods coexpressed both CaBP4 and CaBP5. Our single-cell reverse transcription polymerase chain reaction analysis confirmed the coexpression CaBP1 and CaBP5 in individual RBs from mice of either sex. Additionally, all three splice variants of CaBP1, primarily L-CaBP1, were detected in mouse RBs. Taken together, our study offers a comprehensive overview of the distribution of CaBPs in mouse and human retinal neurons, providing valuable insights into their roles in visual functions.

Jagged1-Notch1 Signaling Pathway Induces M1 Microglia to Disrupt the Barrier Function of Retinal Microvascular Endothelial Cells.

PURPOSE: Microglia-related inflammation is closely linked to the pathogenesis of retinal diseases. The primary objective of this research was to investigate the impact and mechanism of M1 phenotype microglia on the barrier function of retina microvascular endothelial cells. METHODS: Quantitative polymerase chain reactions and western blot techniques were utilized to analysis the mRNA and protein expressions of M1 and M2 markers of human microglial clone 3 cell line (HMC3), as well as the levels of Notch ligands and receptors under the intervention of lipopolysaccharide (LPS) or interleukin (IL)-4. ELISA was utilized to detect the pro-inflammatory and anti-inflammatory cytokines from HMC3 cells. The cellular tight junction and apoptosis of human retinal microvascular endothelial cells (HRMECs) were assessed by western blot and fluorescein isothiocyanate-dextran permeability assay. The inhibitors of Notch1 and RNA interference (RNAi) targeting Jagged1 were used to assess their contribution to the barrier function of vascular endothelial cells. RESULTS: Inducible nitric oxide synthase (iNOS) and IL-1ß were considerably elevated in LPS-treated HMC3, while CD206 and Arg-1 markedly elevated under IL-4 stimulation. The conditioned medium derived from LPS-treated HMC3 cells promoted permeability, diminished the expression of zonula occludens-1 and Occludin, and elevated the expression of Cleaved caspase-3 in HRMECs. RNAi targeting Jagged1 or Notch1 inhibitor could block M1 HMC3 polarization and maintain barrier function of HRMECs. CONCLUSION: Our findings suggest that Jagged1-Notch1 signaling pathway induces M1 microglial cells to disrupt the barrier function of HRMECs, which may lead to retinal diseases.

Exosomal Src from hypoxic vascular smooth muscle cells exacerbates ischemic brain injury by promoting M1 microglial polarization.

Inflammatory response mediated by M1 microglia is a crucial factor leading to the exacerbation of brain injury after ischemic stroke (IS). Under the stimulation of IS, vascular smooth muscle cells (VSMCs) switch to the synthetic phenotype characterized by exosome secretion. Previous studies have shown that exosomes play an important role in the regulation of microglial polarization. We reported that exosomes derived from primary human brain VSMCs under hypoxia (HExos), but not those under normoxia (Exos), significantly promoted primary human microglia (HM1900) shift to M1 phenotype. Proteomic analysis showed that the Src protein enriched in HExos was a potential pro-inflammatory mediator. In vitro experiments showed that the expression of Src and M1 markers were upregulated in HM1900 co-incubated with HExos. However, the Src inhibitor dasatinib (DAS) significantly promoted the transformation of HM1900 phenotype from M1 to M2. In vivo experiments of pMCAO mice also revealed that DAS could effectively inhibit the activation of M1 microglia/macrophages, protect neurons from apoptosis, and improve neuronal function. These data suggested that hypoxic-VSMCs-derived exosomes were involved in post-IS inflammation by promoting M1 microglial polarization through Src transmission. Targeting inhibition of Src potentially acts as an effective strategy for treating brain injury after IS.