Transient charge-driven 3D conformal printing via pulsed-plasma impingement.

Seamless integration of microstructures and circuits on three-dimensional (3D) complex surfaces is of significance and is catalyzing the emergence of many innovative 3D curvy electronic devices. However, patterning fine features on arbitrary 3D targets remains challenging. Here, we propose a facile charge-driven electrohydrodynamic 3D microprinting technique that allows micron- and even submicron-scale patterning of functional inks on a couple of 3D-shaped dielectrics via an atmospheric-pressure cold plasma jet. Relying on the transient charging of exposed sites arising from the weakly ionized gas jet, the specified charge is programmably deposited onto the surface as a virtual electrode with spatial and time spans of ~mm in diameter and ~µs in duration to generate a localized electric field accordantly. Therefore, inks with a wide range of viscosities can be directly drawn out from micro-orifices and deposited on both two-dimensional (2D) planar and 3D curved surfaces with a curvature radius down to ~1 mm and even on the inner wall of narrow cavities via localized electrostatic attraction, exhibiting a printing resolution of ~450 nm. In addition, several conformal electronic devices were successfully printed on 3D dielectric objects. Self-aligned 3D microprinting, with stacking layers up to 1400, is also achieved due to the electrified surfaces. This microplasma-induced printing technique exhibits great advantages such as ultrahigh resolution, excellent compatibility of inks and substrates, antigravity droplet dispersion, and omnidirectional printing on 3D freeform surfaces. It could provide a promising solution for intimately fabricating electronic devices on arbitrary 3D surfaces.

Transboundary migration of Loxostege sticticalis (Lepidoptera: Crambidae) among China, Russia and Mongolia.

BACKGROUND: The beet webworm, Loxostege sticticalis, a worldwide pest of many crops, performs a seasonal migration, causing periodic outbreaks in Asia, Europe and North America. Although long-distance migration is well documented in China, patterns of transboundary migration among China, Russia and Mongolia are largely unknown. We performed a phase analysis of L. sticticalis periodic outbreaks among three countries based on 30 years of historical population data, analyzed the wind systems during migration over boundary regions, and traced the migratory routes in a case study of outbreaks in 2008 by trajectory simulation. RESULTS: Highly synchronized outbreak years of L. sticticalis were observed between China and Mongolia, China and eastern Siberia, China and western Siberia, Mongolia and eastern Siberia, eastern Siberia and western Siberia from 1978 to 2008, indicating possible transboundary migration between these regions. Winds at 300-600 m altitude, where adult migration usually occurs, also showed a high probability of northwestern winds in Haila'er (China), Chita (Russia) and Choybalsan (Mongolia), favoring successful adult migration from these areas to northern and northeastern China. Back trajectory analysis further showed that the first-generation adults that caused the severe outbreak of second-generation larvae in 2008 originated from eastern Siberia, eastern Mongolia, and the boundary regions of China-Russia and China-Mongolia. CONCLUSION: Our findings demonstrated that the source of L. sticticalis outbreaks in northern China was closely related to the outbreaks in Siberia and Mongolia via long-distance transboundary windborne migration. This information will help guide international monitoring and management strategies against this notorious pest. © 2024 Society of Chemical Industry.

Three-Dimensional-Printed Template-Guided Radioactive Seed Brachytherapy via a Submental Approach for Recurrent Base of Tongue and Floor of Mouth Cancer.

Background: This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer. Methods: Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated. Results: The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis. Conclusions: 3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.

Preparation of a Novel Oat ß-Glucan-Chromium(III) Complex and Its Hypoglycemic Effect and Mechanism.

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.

Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells.

Background: Cancer has the highest mortality rate among gynecological cancers and poses a serious threat to women's lives. However, the treatment options for ovarian cancer are still limited, and exploring effective targeted biomarkers is particularly important for predicting and treating ovarian cancer. Therefore, it is necessary to explore the molecular mechanisms of the occurrence and development of ovarian cancer. Methods: This investigation encompassed the analysis of gene expression profiles, measurement of transcription levels of potential target genes in peripheral blood samples from ovarian cancer patients and characterization of the ovarian cancer-related secretory protein sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Through bioinformatics analysis, potential target genes were identified, and their association with overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients was assessed utilizing relevant databases. Subsequently, differences in target gene expression in ovarian cancer tissue samples were validated through protein blotting and quantitative real-time PCR (qRT-qPCR). Cell proliferation assays using the cell count kit-8 (CCK-8) method, as well as transwell chamber assay and pre coated matrix gel chamber assay were employed to elucidate the role of SMPDL3B in ovarian cancer cell migration and invasion. Results: This study revealed a substantial upregulation of SMPDL3B in the serum of ovarian cancer patients, correlating with an unfavorable prognosis. High SMPDL3B expression was linked not only to increased proliferation of ovarian cancer cells, but also enhanced migration and invasion. Remarkably, the knockdown the human alkaline ceramidase 2 (ACER2) gene in cancer cells with heightened SMPDL3B expression significantly inhibited cell proliferation, migration, and invasion induced by SMPDL3B activation (P<0.05), highlighting the functional interplay between ACER2 and SMPDL3B in ovarian cancer. Conclusions: In summary, this study proposes SMPDL3B as a prognostic marker for ovarian cancer, with implications for potential therapeutic intervention targeting the ACER2-SMPDL3B axis.

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

Pain and daily interference among reproductive-age women with myofascial pelvic pain: Serial mediation roles of kinesiophobia, self-efficacy and pain catastrophizing.

BACKGROUND: Myofascial pelvic pain (MFPP), which is identified by tender points in the pelvic floor musculature, is a prevalent source of chronic pelvic pain in women. It may lead to physical and mental exhaustion, reproductive concerns, and coping difficulties in daily life and work than the disease itself. Pain-related cognitive processes can affect pain relief and quality of life. Kinesiophobia, self-efficacy and pain catastrophizing are frequently treated as mediators between pain and its related consequences. Greater kinesiophobia and pain catastrophizing have been shown to be associated with adverse functional outcomes, while higher self-efficacy has been related with improved quality of life. Regarding MFPP in females of childbearing age, it remains unclear whether the effects of kinesiophobia, self-efficacy and pain catastrophizing on daily interference are direct or indirect; the influence on each variable is, therefore, not entirely evident. AIM: The present study aimed to evaluate the relationship between pain and daily interference in reproductive-age women with MFPP through kinesiophobia, self-efficacy and pain catastrophizing, as well as to identify areas for future investigation and intervention based on the data collected from this population. METHODS: This is a multi-center cross-sectional study. The study was conducted from November 15, 2022 to November 10, 2023, 202 reproductive-age women with MFPP were recruited from 14 hospitals in ten provinces of China. The demographic variables, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain Self-Efficacy Questionnaire, and Pain Catastrophizing Scale were used to measure the participants' related information. The data was described and analyzed using Descriptive analyses, Pearson correlation analysis, and Serial mediation modeling. RESULTS: Pain not only had a direct positive impact (B = 0.575; SE = 0.081; 95%CI: LL = 0.415, UL = 0.735) on daily interference, but also had an indirect impact on daily interference through the independent mediating role of pain catastrophizing (B = 0.088; SE = 0.028; 95%CI: LL = 0.038, UL = 0.148), the chain mediating of kinesiophobia and catastrophizing (B = 0.057; SE = 0.019; 95%CI: LL = 0.024, UL = 0.098), and the four-stage serial mediating of kinesiophobia, self-efficacy and catastrophizing (B = 0.013; SE = 0.006; 95%CI: LL = 0.003, UL = 0.027). The proposed serial mediation model showed a good fit with the collected data. CONCLUSION: The findings illustrate the significance of addressing pain catastrophizing and kinesiophobia (especially catastrophizing), and increasing self-efficacy in pain therapy, and suggest that functional recovery be integrated into pain therapy for reproductive-age women suffering from MFPP.

Ionic Current Saturation Enabled by Cation Gating Effect in Metal-Organic-Framework Membranes.

Ion transport through nanoporous two-dimensional (2D) membranes is predicted to be tunable by controlling the charging status of the membranes' planar surfaces, the behavior of which though remains to be assessed experimentally. Here we investigate ion transport through intrinsically porous membranes made of 2D metal-organic-framework layers. In the presence of certain cations, we observe a linear-to-nonlinear transition of the ionic current in response to the applied electric field, the behavior of which is analogous to the cation gating effect in the biological ion channels. Specifically, the ionic currents saturate at transmembrane voltages exceeding a few hundreds of millivolts, depending on the concentration of the gating cations. This is attributed to the binding of cations at the membranes' surfaces, tuning the charging states there and affecting the entry/exit process of translocating ions. Our work also provides 2D membranes as candidates for building nanofluidic devices with tunable transport properties.

Characteristics and immune functions of the endogenous CRISPR-Cas systems in myxobacteria.

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

Rare Presentation of Melanoma Recurrences With Diffuse Subcutaneous Intravascular Lesions: A Novel In-Transit Metastases Pattern.

ABSTRACT: In 4%-11% of cases, melanoma recurrences present as in-transit (IT) metastases, and their prognosis is quite poor. Consequently, an early diagnosis and treatment of IT metastasis assume paramount significance. Despite this, the diagnosis of cutaneous IT metastases persistently presents a formidable challenge due to the diversity in clinical and dermoscopic characteristics. We provide a novel melanoma IT metastases pattern with interesting dermoscopic features and magnetic resonance imaging via presenting an unusual case characterized by diffuse subcutaneous intravascular lesions to supplement the understanding of cutaneous melanoma IT metastases.

The novel DNA methylation marker FIBIN suppresses non-small cell lung cancer metastasis by negatively regulating ANXA2.

OBJECTIVES: The clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. METHODS: Quantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co-IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. RESULTS: We reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of ß-catenin by reducing the binding activity of GSK3ß with ANXA2 while promoting interaction between GSK3ß and ß-catenin. CONCLUSION: Our findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.

Efficient adsorption of rhodamine B using synthesized Mg-Al hydrotalcite/ sodium carboxymethylcellulose/ sodium alginate hydrogel spheres: Performance and mechanistic analysis.

In this study, the sodium dodecyl sulfate intercalated modified magnesium-aluminum hydrotalcite/sodium alginate/sodium carboxymethylcellulose (modified LDHs/SA/CMC) composite gel spheres were synthesized and their efficacies in adsorbing the cationic dye rhodamine B (RhB) from aqueous solutions were evaluated. The effects of adsorption time, pH and temperature on the adsorption of RhB by spheres were investigated. Remarkably, the modified LDHs/SA/CMC gel spheres achieved adsorption equilibrium after 600 min at 25 °C, and the removal rate of RhB at 60 mg/L reached 91.49 % with the maximum adsorption capacity of 59.64 mg/g. The gel spheres maintained over 80 % efficacy across four adsorption cycles. Kinetic and isotherm analyses revealed that the adsorption of RhB conformed to the secondary kinetic model and the Langmuir isotherm, indicating a spontaneous and exothermic nature of the adsorption process. The adsorption mechanisms of modified LDHs/SA/CMC gel spheres on RhB dyes include electrostatic adsorption, hydrogen bonding and hydrophobic interactions. In conclusion, modified LDHs/SA/CMC gel sphere is a green, simple, recyclable and efficient adsorbent, which is expected to be widely used for the treatment of cationic dye wastewater.

Effect of Cytochrome P450 3A4 on Tissue Distribution of Humantenmine, Koumine, and Gelsemine, three Alkaloids from the Toxic Plant Gelsemium.

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5minutes after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20minutes. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

Effects of micro- and nano-plastics on growth, antioxidant system, DMS, and DMSP production in Emiliania huxleyi.

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.

Air pollution, life's essential 8, and risk of severe non-alcoholic fatty liver disease among individuals with type 2 diabetes.

BACKGROUND: The impacts of long-term exposure to air pollution on the risk of subsequent non-alcoholic fatty liver disease (NAFLD) among participants with type 2 diabetes (T2D) is ambiguous. The modifying role of Life's Essential 8 (LE8) remains unknown. METHODS: This study included 23,129 participants with T2D at baseline from the UK Biobank. Annual means of nitrogen dioxide (NO2), nitrogen oxides (NOX), and particulate matter (PM2.5, PM2.5-10, PM10) were estimated using the land-use regression model for each participant. The associations between exposure to air pollution and the risk of severe NAFLD were evaluated using Cox proportional hazard models. The effect modification of LE8 was assessed through stratified analyses. RESULTS: During a median 13.6 years of follow-up, a total of 1,123 severe NAFLD cases occurred. After fully adjusting for potential covariates, higher levels of PM2.5 (hazard ratio [HR] = 1.12, 95%CI:1.02, 1.23 per interquartile range [IQR] increment), NO2 (HR = 1.15, 95%CI:1.04, 1.27), and NOX (HR = 1.08, 95%CI:1.01, 1.17) were associated with an elevated risk of severe NAFLD. In addition, LE8 score was negatively associated with the risk of NAFLD (HR = 0.97, 95% CI: 0.97, 0.98 per point increment). Compared with those who had low air pollution and high LE8, participants with a high air pollution exposure and low LE8 had a significantly higher risk of severe NAFLD. CONCLUSIONS: Our findings suggest that long-term exposure to air pollution was associated with an elevated risk of severe NAFLD among participants with T2D. A lower LE8 may increase the adverse impacts of air pollution on NAFLD.

Recent drug development of dorzagliatin, a new glucokinase activator, with the potential to treat Type 2 diabetes: A review study.

Type 2 diabetes mellitus (T2DM) is a complicated disease related to metabolism that results from resistance to insulin and sustained hyperglycemia. Traditional antidiabetic drugs cannot meet the demand of different diabetes patients for reaching the glycemic targets; thus, the identification of new antidiabetic drugs is urgently needed for the treatment of T2DM to enhance glycemic control and the prognosis of patients suffering from T2DM. Recently, glucokinase (GK) has attracted much attention and is considered to be an effective antidiabetic agent. Glucokinase activators (GKA) represented by dorzagliatin could activate GK and mimic its function that triggers a counter-regulatory response to blood glucose changes. Dorzagliatin has shown great potential for glycemic control in diabetic patients in a randomized, double-blind, placebo-controlled Phase 3 trial (SEED study) and had a favorable safety profile and was well tolerated (DAWN study). In the SEED study, dorzagliatin significantly reduced glycosylated hemoglobin (HbA1c) by 1.07% and postprandial blood glucose by 2.83 mol/L, showing the great potential of this drug to control blood glucose in diabetic patients, with good safety and good tolerance. An extension of the SEED study, the DREAM study, confirmed that dorzagliatin monotherapy significantly improved 24-h glucose variability and increased time in range (TIR) to 83.7% over 46 weeks. Finally, the clinical study of dorzagliatin combined with metformin (DAWN study) confirmed that dorzagliatin could significantly reduce HbA1c by 1.02% and postprandial blood glucose by 5.45 mol/L. The current review summarizes the development of GK and GKA, as well as the prospects, trends, applications, and shortcomings of these treatments, especially future directions of clinical studies of dorzagliatin.

Peritendinous Submembrane Access Technique for Management of Acute Ruptures of the Achilles Tendon: A Retrospective Study of 249 Cases.

OBJECTIVE: Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re-rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS-PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. METHODS: This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS-PSAT at our institution and were followed up for 8-48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), associated with local complications and isokinetic tests. RESULTS: None of the patients had infection, necrosis, or sural nerve injury. Re-rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS-AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). CONCLUSION: The MIS-PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re-rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.