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Kaixuan Zhao,1,* Siqi Pu,2,* Liyun Sun,1 Dongmei Zhou1 1Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 10010, People’s Republic of China; 2School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyun Sun, Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art Musuem Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email doctorsunny@sina.cn Dongmei Zhou, Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art musuem Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email 52176857@163.comPurpose: In this study, we aimed to report the biological characteristics of the first successful synthesis of gentiopicroside-loaded chitosan nanoparticles and to evaluate the therapeutic effects and preliminary mechanisms of gentiopicrin-loaded chitosan on psoriasis-like cell and mouse models.Methods: Gentiopicroside-loaded chitosan nanoparticles (CHI-GEN) were prepared, and their biological characteristics were evaluated. HaCaT keratinocytes were stimulated with TNF-α to establish a psoriatic keratinocyte model. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. mRNA levels of K17, VEGF A, and IL-6 and IL-23A were detected using qRT-PCR. These tests were used to preliminarily assess the effects of CHI-GEN on keratinocyte proliferation and inflammation. Imiquimod was used to construct a psoriasis-like mice model. The severity of psoriasis was scored based on the psoriasis area severity index (PASI), H&E staining was used to observe the histological changes and the level of inflammation and cell proliferation of skin lesions was evaluated by measuring the mRNA levels of K17, IL-23A, and IL-17A using qRT-PCR.Results: The average particle size of CHI-GEN nanoparticles was approximately 100 nm, and the zeta potential was 2.69 ± 0.87 mV. The cumulative release was 67.2% in solutions of pH 5.5 at 24 h. GEN reduced TNF-α-induced excessive proliferation of HaCaT keratinocytes and downregulated mRNA levels of K17, VEGF A, and inflammatory cytokines IL-6 and IL-23A, which was more obvious in the CHI-GEN treatment group. Additionally, CHI-GEN significantly improved the severity of skin lesions in psoriasis-like mice and downregulated the mRNA expressions of IL-6, IL-23A, and IL-17A in mice skin lesions.Conclusion: In conclusion, we successfully prepared gentiopicrin-chitosan nanoparticles. Our results show that these nanoparticles have anti-psoriasis activity, inhibits keratinocyte proliferation and improves symptoms in psoriasis model mice and can be used to develop an effective strategy for the treatment of psoriasis.Keywords: chitosan, nanoparticles, gentiopicroside, chitosan-loaded nano cream for external use, psoriasis, proliferation and inflammation

IntroductionIn recent years, the Pipeline embolization device (PED) has been widely used in the embolization of intracranial aneurysms, but there are some inconsistent findings on whether its efficacy and safety are superior to those of traditional coils embolization (coils alone, stent-assisted coils and balloon-assisted coils). The purpose of this meta-analysis was to evaluate the safety and efficacy of PED in intracranial aneurysm embolization by comparing with traditional coils.MethodsWe systematically searched PubMed, Embase, Web of Science, and The Cochrane Library databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the efficacy of PED with traditional coils in intracranial aneurysm embolization published before April 1, 2022. The endpoints observed in this meta-analysis were procedure-related intracranial hemorrhage, procedure-related intracranial ischemia, other procedure-related complications (e.g., aneurysm rupture, neurological impairment, etc.), retreatment rate, complete occlusion (100%) of the aneurysm at the last follow-up, and favorable functional outcome (MRS ≤ 2).ResultsA total of 10 studies with a total of 1,400 patients (PED group: 576 and Traditional coils: 824) were included in this meta-analysis. A comprehensive analysis of the included literature showed that the PED group had a higher rate of complete aneurysm occlusion [OR = 2.62, 95% Cl (1.94, 3.55), p < 0.00001] and Lower re-treatment rate [OR = 0.20, 95% Cl (0.12, 0.34 p < 0.00001)] compared with the traditional coil embolization group at the last follow-up. In terms of procedure-related intracranial hemorrhage [OR = 3.04, 95% Cl (1.08, 8.57), p = 0.04] and other procedure-related complications [OR = 2.91, 95% Cl (1.48, 5.57), p = 0.002], the incidence of PED was higher than that of the traditional coil embolization group. Moreover, in terms of favorable functional outcome [OR = 0.4, 95% Cl (0.22, 0.71), p = 0.002] of patients at the last follow-up, the PED group was lower than the traditional coil embolization group. There was no statistically significant between the two groups in terms of surgery-related intracranial ischemia complications [OR = 0.88, 95% Cl (0.47, 1.64), p = 0.68].ConclusionPED had higher rates of complete aneurysm occlusion and lower rates of aneurysm retreatment compared with traditional coils, but traditional coils was superior to the PED group in terms of procedure-related intracranial hemorrhage complication and other procedure-related complications (aneurysm rupture, neurological impairment), and favorable functional outcome (mRS ≤ 2). This result still needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022325673.

HIGHLIGHTSA deep learning algorithm with an improved lightweight network was used to identify apple fruit.Multiscale pooling was used to reduce the image size and enrich the features.Compound scaling was used to scale the basic network.The optimal compound scaling coefficient for apple identification was obtained with the WOA algorithm.The proposed method achieved an average recognition precision rate of 94.43% and a speed of 0.051s.ABSTRACT. Accurate fruit identification is the basis for automating the operation of orchard production. To better apply the identification model in mobile devices so that venue becomes a less restrictive factor for application, this study proposes an apple fruit identification method based on an improved lightweight network named “MobileNetV3-Small.” The whale optimization algorithm was introduced to improve the model by obtaining an optimal compound-scaling coefficient for the MobileNetV3-Small network. A multiscale pooling approach was used for fruit recognition, comprising operations such as lossless scaling and feature extraction on sample images. The obtained images were then inputted into the model for recognition and classification. The experimental process was conducted on an apple data set. The test results show that the multiclass average precision of apple recognition using this model was 94.43% and the running time of recognition was 0.051 s per image. Both indicators outperformed the control network models of “MobileNetV3-Small,” ResNet-50, and VGG-19. This model is 14.63% more accurate and 1.95 times quicker on average in identification than the next best model. These findings indicate that the method can realize high-efficiency and high-precision recognition of apples with high stability and portability, which lays a good foundation for the mechanization of repetitive operations such as orchard yield estimation, fruit labeling, and fruit picking. Keywords: Apple recognition, Compound scaling, Deep learning algorithm, Lightweight network, Yield estimation.

We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.

Significance We provide evidence of a mechanistic link between ALS and T2DM. Our data show that a subgroup of ALS-T2DM patients have sera that enhance CaV1 channel-mediated Ca2+ influx and exaggerate [Ca2+]i. These effects occur because the sera accommodate cytotoxic IgG autoantibodies that immunocapture CaVα2δ1 subunits. As a consequence, impairments in [Ca2+]i dynamics, mitochondrial function, insulin secretion, and cell viability appear. We could clarify not only the identity of this serum factor but also the molecular mechanisms underlying its effects on the islet cells. Our findings may lay the foundation for a treatment strategy for this complex and severe group of diabetic patients., Patients with amyotrophic lateral sclerosis (ALS) often show hallmarks of type 2 diabetes mellitus (T2DM). However, the causal link between ALS and T2DM has remained a mystery. We now demonstrate that 60% of ALS patients with T2DM (ALS-T2DM) have sera that exaggerated K+-induced increases in cytosolic free Ca2+ concentration ([Ca2+]i) in mouse islet cells. The effect was attributed to the presence of pathogenic immunoglobulin Gs (IgGs) in ALS-T2DM sera. The pathogenic IgGs immunocaptured the voltage-dependent Ca2+ (CaV) channel subunit CaVα2δ1 in the plasma membrane enhancing CaV1 channel-mediated Ca2+ influx and [Ca2+]i, resulting in impaired mitochondrial function. Consequently, impairments in [Ca2+]i dynamics, insulin secretion, and cell viability occurred. These data reveal that patients with ALS-T2DM carry cytotoxic ALS-T2DM-IgG autoantibodies that serve as a causal link between ALS and T2DM by immunoattacking CaVα2δ1 subunits. Our findings may lay the foundation for a pharmacological treatment strategy for patients suffering from a combination of these diseases.

Significance We reveal that increased expression of CaV3.1 channels in rat islets selectively impairs first-phase glucose-stimulated insulin secretion. This deterioration is recapitulated in human islets. Its causal role in diabetes development is clearly manifested in an in vivo diabetic model. Mechanistically, this is due to reduction of phosphorylated FoxO1 in the cytoplasm, elevated FoxO1 nuclear retention, and decreased syntaxin 1A, SNAP-25, and synaptotagmin III in a CaV3.1 channel- and calcineurin-dependent manner. Our findings suggest that elevated expression of CaV3.1 channels in pancreatic islets drives FoxO1-mediated down-regulation of exocytotic proteins resulting in the diabetic phenotypes of impaired insulin secretion and aberrant glucose homeostasis. This causal connection pinpoints β cell CaV3.1 channels as a potential druggable target for antidiabetes therapy., Voltage-gated calcium 3.1 (CaV3.1) channels are absent in healthy mouse β cells and mediate minor T-type Ca2+ currents in healthy rat and human β cells but become evident under diabetic conditions. Whether more active CaV3.1 channels affect insulin secretion and glucose homeostasis remains enigmatic. We addressed this question by enhancing de novo expression of β cell CaV3.1 channels and exploring the consequent impacts on dynamic insulin secretion and glucose homeostasis as well as underlying molecular mechanisms with a series of in vitro and in vivo approaches. We now demonstrate that a recombinant adenovirus encoding enhanced green fluorescent protein–CaV3.1 subunit (Ad-EGFP-CaV3.1) efficiently transduced rat and human islets as well as dispersed islet cells. The resulting CaV3.1 channels conducted typical T-type Ca2+ currents, leading to an enhanced basal cytosolic-free Ca2+ concentration ([Ca2+]i). Ad-EGFP-CaV3.1-transduced islets released significantly less insulin under both the basal and first phases following glucose stimulation and could no longer normalize hyperglycemia in recipient rats rendered diabetic by streptozotocin treatment. Furthermore, Ad-EGFP-CaV3.1 transduction reduced phosphorylated FoxO1 in the cytoplasm of INS-1E cells, elevated FoxO1 nuclear retention, and decreased syntaxin 1A, SNAP-25, and synaptotagmin III. These effects were prevented by inhibiting CaV3.1 channels or the Ca2+-dependent phosphatase calcineurin. Enhanced expression of β cell CaV3.1 channels therefore impairs insulin release and glucose homeostasis by means of initial excessive Ca2+ influx, subsequent activation of calcineurin, consequent dephosphorylation and nuclear retention of FoxO1, and eventual FoxO1-mediated down-regulation of β cell exocytotic proteins. The present work thus suggests an elevated expression of CaV3.1 channels plays a significant role in diabetes pathogenesis.