Molecular cytogenetic characterization of 9 populations of four species in the genus Polygonatum (Asparagaceae).

To characterize the chromosomes of the four species of Polygonatum Miller, 1754, used in traditional Chinese medicine, P.cyrtonema Hua, 1892, P.kingianum Collett et Hemsley, 1890, P.odoratum (Miller, 1768) Druce, 1906, and P.sibiricum Redouté, 1811, and have an insight into the karyotype variation of the genus Polygonatum, fluorescence in situ hybridization (FISH) with 5S and 45S rDNA oligonucleotide probes was applied to analyze the karyotypes of 9 populations of the four species. Detailed molecular cytogenetic karyotypes of the 9 populations were established for the first time using the dataset of chromosome measurements and FISH signals of 5S and 45S rDNA. Four karyotype asymmetry indices, CVCI, CVCL, MCA and Stebbins' category, were measured to elucidate the asymmetry of the karyotypes and karyological relationships among species. Comparison of their karyotypes revealed distinct variations in the karyotypic parameters and rDNA patterns among and within species. The basic chromosome numbers detected were x = 9, 11 and 13 for P.cyrtonema, x = 15 for P.kingianum, x = 10 and 11 for P.odoratum, and x = 12 for P.sibiricum. The original basic chromosome numbers of the four species were inferred on the basis of the data of this study and previous reports. All the 9 karyotypes were of moderate asymmetry and composed of metacentric, submetacentric and subtelocentric chromosomes or consisted of two of these types of chromosomes. Seven populations have one locus of 5S rDNA and two loci of 45S rDNA, and two populations added one 5S or 45S locus. The karyological relationships among the four species revealed by comparison of rDNA patterns and PCoA based on x, 2n, TCL, CVCI, MCA and CVCL were basically accordant with the phylogenetic relationships revealed by molecular phylogenetic studies. The mechanisms of both intra- and inter-specific dysploidy in Polygonatum were discussed based on the data of this study and literature.

Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia.

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.

Microwave coupled Zeeman splitting spectroscopy of a cesium nPJ Rydberg atom.

We perform measurements of microwave spectra of cesium Rydberg 51S1/2 → 51PJ transitions with the linewidth approaching the Fourier limit. A two-photon scheme excites the ground-state atoms to the Rydberg 51S1/2 state, and a weak microwave photon couples the Rydberg transition of 51S1/2 → 51PJ. The hyperfine structure of 51P1/2 can be clearly resolved with a narrow linewidth microwave spectra by using the method of ion detection. Furthermore, we investigate the Zeeman effect of the 51P1/2,3/2 state. The theoretical calculations reproduce the measurement well. Our experimental measurements provide a reliable technical solution for the investigation of high angular momentum Rydberg states, which is conducive to further realizing the coherent manipulation of Rydberg energy levels and improving the sensitivity of electromagnetic field measurement.

Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ETA ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half-life (t1/2 ) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET-1 concentrations were dose-proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high-fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.

Study on the Thermal Stability of the Sweet-Tasting Protein Brazzein Based on Its Structure-Sweetness Relationship.

Brazzein (Brz) is a sweet-tasting protein composed of 54 amino acids and is considered as a potential sugar substitute. The current methods for obtaining brazzein are complicated, and limited information is available regarding its thermal stability. In this study, we successfully expressed recombinant brazzein, achieving a sweetness threshold of 15.2 µg/mL. Subsequently, we conducted heat treatments at temperatures of 80, 90, 95, and 100 °C for a duration of 2 h to investigate the structural changes in the protein. Furthermore, we employed hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) to analyze the effect of heating on the protein structure-sweetness relationships. Our results indicated that the thermal inactivation process primarily affects residues 6-14 and 36-45 of brazzein, especially key residues Tyr8, Tyr11, Ser14, Glu36, and Arg43, which are closely associated with its sweetness. These findings have significant implications for improving the thermal stability of brazzein.

Recent advances in microbial fuel cell-based self-powered biosensors: a comprehensive exploration of sensing strategies in both anode and cathode modes.

With the rapid development of society, it is of paramount importance to expeditiously assess environmental pollution and provide early warning of toxicity risks. Microbial fuel cell-based self-powered biosensors (MFC-SPBs) have emerged as a pivotal technology, obviating the necessity for external power sources and aligning with the prevailing trends toward miniaturization and simplification in biosensor development. In this case, vigorous advancements in MFC-SPBs have been acquired in past years, irrespective of whether the target identification event transpires at the anode or cathode. The present article undertakes a comprehensive review of developed MFC-SPBs, categorizing them into substrate effect and microbial activity effect based on the nature of the target identification event. Furthermore, various enhancement strategies to improve the analytical performance like accuracy and sensitivity are also outlined, along with a discussion of future research trends and application prospects of MFC-SPBs for their better developments.

Highly Robust Room-Temperature Interfacial Ferromagnetism in Ultrathin Co2Si Nanoplates.

The reduced dimensionality and interfacial effects in magnetic nanostructures open the feasibility to tailor magnetic ordering. Here, we report the synthesis of ultrathin metallic Co2Si nanoplates with a total thickness that is tunable to 2.2 nm. The interfacial magnetism coupled with the highly anisotropic nanoplate geometry leads to strong perpendicular magnetic anisotropy and robust hard ferromagnetism at room temperature, with a Curie temperature (TC) exceeding 950 K and a coercive field (HC) > 4.0 T at 3 K and 8750 Oe at 300 K. Theoretical calculations suggest that ferromagnetism originates from symmetry breaking and undercoordinated Co atoms at the Co2Si and SiO2 interface. With protection by the self-limiting intrinsic oxide, the interfacial ferromagnetism of the Co2Si nanoplates exhibits excellent environmental stability. The controllable growth of ambient stable Co2Si nanoplates as 2D hard ferromagnets could open exciting opportunities for fundamental studies and applications in Si-based spintronic devices.

Hydrogen sulfide mitigates memory impairments via the restoration of glutamatergic neurons in a mouse model of hemorrhage shock and resuscitation.

Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased ß power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored ß power. Moreover, hydrogen sulfide (H2S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H2S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased ß power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H2S may be useful therapeutic approaches for improving memory deficits following HSR.

An Adaptive Hammerstein Model for FES-Induced Torque Prediction Based on Variable Forgetting Factor Recursive Least Squares Algorithm.

Modeling the muscle response to functional electrical stimulation (FES) is an important step during model-based FES control system design. The Hammerstein structure is widely used in simulating this nonlinear biomechanical response. However, a fixed relationship cannot cope well with the time-varying property of muscles and muscle fatigue. In this paper, we proposed an adaptive Hammerstein model to predict ankle joint torque induced by electrical stimulation, which used variable forgetting factor recursive least squares (VFFRLS) method to update the model parameters. To validate the proposed model, ten healthy individuals were recruited for short-duration FES experiments, ten for long-duration FES experiments, and three stroke patients for both. The isometric ankle dorsiflexion torque induced by FES was measured, and then the test performance of the fixed-parameter Hammerstein model, the adaptive Hammerstein model based on fixed forgetting factor recursive least squares (FFFRLS) and the adaptive Hammerstein model based on VFFRLS was compared. The goodness of fit, root mean square error, peak error and success rate were applied to evaluate the accuracy and stability of the model. The results indicate a significant improvement in both the accuracy and stability of the proposed adaptive model compared to the fixed-parameter model and the adaptive model based on FFFRLS. The proposed adaptive model enhances the ability of the model to cope with muscle changes.

Time-varying and speed-matched model for the evaluation of stroke-induced changes in ankle mechanics.

The ankle mechanics (stiffness and moment) are modulated continuously when interacting with the environment during human walking. However, it remains unclear how ankle mechanics vary with walking speeds, and how they are affected by stroke. This study aimed to determine time-varying ankle stiffness and moment in stroke participants during walking, comparing them with healthy participants at matched speeds. A motion capture system, surface electromyography (EMG) system and force plates were used to measure biomechanics of seven healthy participants walking at 5 controlled speeds and ten patients with stroke at self-selected speeds. The ankle moment and stiffness during the stance phase were calculated using an EMG-driven musculoskeletal model. Surface equations of ankle moment and stiffness in healthy participants, with walking speed and stance phase as variables, were proposed based on polynomial fitting. Results showed that as walking speed increased, there was an increase in the ankle stiffness and moment of healthy participants during 77 %-89 % and 63 %-91 % of stance phase, respectively. Patients with stroke had lower ankle stiffness and moment at self-selected walking speed than healthy participants at 1.04 m/s walking speed during 52 %-87 % and 52 %-91 % of stance phase, respectively. At matched walking speed, the peak values of ankle stiffness and moment in patients with stroke were significantly less than those in healthy participants (p = 0.007; p = 0.028, respectively). This study proposes a novel approach to evaluate the ankle mechanics of patients with stroke using the speed-matched model of healthy participants and may provide insights into understanding speed-dependent movement mechanisms of human walking.

Isometric Plantarflexion Moment Prediction Based on a Compartment-specific HD-sEMG-driven Musculoskeletal Model.

OBJECTIVE: electromyogram (EMG)-driven musculoskeletal models have been widely used to investigate human movements while existing EMG-driven models commonly neglect regional heterogeneity in anatomy and activation within a skeletal muscle. To consider neuromuscular compartment anatomy and activation, a subject- and compartment-specific EMG-driven model was developed for isometric plantarflexion moment prediction. METHODS: the model was hill-type consisting of gastrocnemius medialis, gastrocnemius lateralis, and soleus around the ankle joint, and each muscle was discretised into four compartments. The moment arms of each compartment were determined using magnetic resonance imaging and the compartment activation was calculated based on high-density surface EMG signals. And the hill-type compartment parameters were tuned in a calibration process. The developed compartment-specific model and a generic EMG-driven model were examined by comparing their predicted net ankle moments with measurements obtained while subjects performed isometric plantarflexion tasks at different contraction levels. RESULTS: compared to the generic EMG-driven model, the isometric plantarflexion moment prediction using the compartment-specific model was more accurate at all contraction levels, with the average prediction error decreasing from average 13.81% to 10.11%. The contraction of each compartment was found to be generally non-uniform at all contraction levels. CONCLUSION: the developed compartment-specific model enabled accurate prediction of isometric plantarflexion moment and the simulation of non-uniform muscular contraction, which is more physiologically appropriate than the existing EMG-driven models. SIGNIFICANCE: the proposed compartment-specific formulation opens new perspectives for subject-specific musculoskeletal modelling, which has great potential in understanding regional characteristics of the neuromuscular activities.

Trajectory Deformation-Based Multi-Modal Adaptive Compliance Control for a Wearable Lower Limb Rehabilitation Robot.

Adaptive compliance control is critical for rehabilitation robots to cope with the varying rehabilitation needs and enhance training safety. This article presents a trajectory deformation-based multi-modal adaptive compliance control strategy (TD-MACCS) for a wearable lower limb rehabilitation robot (WLLRR), which includes a high-level trajectory planner and a low-level position controller. Dynamic motion primitives (DMPs) and a trajectory deformation algorithm (TDA) are integrated into the high-level trajectory planner, generating multi-joint synchronized desired trajectories through physical human-robot interaction (pHRI). In particular, the amplitude modulation factor of DMPs and the deformation factor of TDA are adapted by a multi-modal adaptive regulator, achieving smooth switching of human-dominant mode, robot-dominant mode, and soft-stop mode. Besides, a linear active disturbance rejection controller is designed as the low-level position controller. Four healthy participants and two stroke survivors are recruited to conduct robot-assisted walking experiments using the TD-MACCS. The results show that the TD-MACCS can smoothly switch three control modes while guaranteeing trajectory tracking accuracy. Moreover, we find that appropriately increasing the upper bound of the deformation factor can enhance the average walking speed (AWS) and root mean square of trajectory deviation (RMSTD).

Heatwave characteristics complicate the association between PM2.5 components and schizophrenia hospitalizations in a changing climate: Leveraging of the individual residential environment.

BACKGROUND: In the era characterized by global environmental and climatic changes, understanding the effects of PM2.5 components and heatwaves on schizophrenia (SCZ) is essential for implementing environmental interventions at the population level. However, research in this area remains limited, which highlights the need for further research and effort. We aim to assess the association between exposure to PM2.5 components and hospitalizations for SCZ under different heatwave characteristics. METHODS: We conducted a 16 municipalities-wide, individual exposure-based, time-stratified, case-crossover study from January 1, 2017, to December 31, 2020, encompassing 160736 hospitalizations in Anhui Province, China. Daily concentrations of PM2.5 components were obtained from the Tracking Air Pollution in China dataset. Conditional logistic regression models were used to investigate the association between PM2.5 components and hospitalizations. Additionally, restricted cubic spline models were used to identify protective thresholds of residential environment in response to environmental and climate change. RESULTS: Our findings indicate a positive correlation between PM2.5 and its components and hospitalizations. Significantly, a 1 µg/m3 increase in black carbon (BC) was associated with the highest risk, at 1.58% (95%CI: 0.95-2.25). Exposure to heatwaves synergistically enhanced the impact of PM2.5 components on hospitalization risks, and the interaction varied with the intensity and duration of heatwaves. Under the 99th percentile heatwave events, the impact of PM2.5 and its components on hospitalizations was most pronounced, which were PM2.5 (2-4d: 4.59%, 5.09%, and 5.09%), sulfate (2-4d: 21.73%, 23.23%, and 25.25%), nitrate (2-4d: 17.51%, 16.93%, and 20.31%), ammonium (2-4d: 27.49%, 31.03%, and 32.41%), organic matter (2-4d: 32.07%, 25.42%, and 24.48%), and BC (2-4d: 259.36%, 288.21%, and 152.52%), respectively. Encouragingly, a protective effect was observed when green and blue spaces comprised more than 17.6% of the residential environment. DISCUSSION: PM2.5 components and heatwave exposure were positively associated with an increased risk of hospitalizations, although green and blue spaces provided a mitigating effect.

Toxicity of common biocides used in aquaculture to embryos and larvae of Brachymystax tsinlingensis Li.

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC50 ) values of the embryos and larvae were 1.71 and 0.22 mg l-1 for copper and 2.57 and 2.72 mg l-1 for zinc, respectively, whereas the MB LC50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l-1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l-1 for embryos and 0.03, 0.03 and 1.78 mg l-1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l-1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l-1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration.

Hepatocyte nuclear factor 1B deletion, but not intragenic mutation, might be more susceptible to hypomagnesemia.

AIMS: HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. MATERIALS AND METHODS: Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. RESULTS: Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). CONCLUSIONS: Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.

A Randomized, Single-Dose, Parallel-Controlled Phase 1 Clinical Comparison of an Omalizumab Biosimilar Candidate with Reference Omalizumab in Healthy Chinese Male Volunteers.

This study evaluated the bioequivalence of omalizumab, a humanized monoclonal antibody against immunoglobulin-E (IgE), with one of its biosimilar candidates. The study was designed as a randomized, double-blind, parallel-controlled trial. A total of subjects who met the inclusion criteria and did not meet the exclusion criteria were dynamically randomly assigned to receive the test drug or the reference drug with a single subcutaneous injection of 150 mg by the minimization method. The test group and the reference group had similar demographic characteristics and baseline characteristics of total IgE. The 90% confidence interval of the geometric average ratio of the area under the serum concentration-time curve from the time 0 to the time of last quantifiable concentration, the area under the serum concentration curve from time 0 to infinity, and the maximum observed serum concentration between the 2 groups were within 80%-125%, showing bioequivalence. The changing trend of total and free IgE in the 2 groups was similar after administration, proving the pharmacodynamic similarity. The 2 groups had no significant difference in the positive rate of antidrug antibodies, and the total positive rate of neutralizing antibodies was 0. The incidence of treatment-emergent adverse events and treatment-related adverse events were similar between the 2 groups, with no serious adverse events. This study shows that the test drug had similar pharmacokinetics, immunogenicity, and safety to the reference omalizumab in healthy male subjects.

Preparation of a novel expandable konjac fiber at different freezing temperatures and exploration of its digestion regulation functions.

A new form of konjac fiber was successfully prepared, and it could instantaneously expand when in contact with the digestive fluid. The expanded konjac fiber could inhibit the digestion of the ingested food by competing with the substrate for digestive enzymes and space. The konjac fiber with desirable physical properties was obtained at 4 different freezing temperatures (-20 °C, -40 °C, -80 °C, and -196 °C), and the digestion regulation mechanisms of these fibers were systematically explored. The results showed that the konjac fiber prepared at -20 °C displayed an outstanding performance in delaying gastric emptying and preventing intestinal starch hydrolysis, while the fiber prepared under liquid nitrogen conditions (-196 °C) showed the weakest digestion regulation ability. However, the digestion regulation ability of this novel fiber was highly related to the food rheological property, and it exhibited a stronger interference effect on high-viscosity food. Our novel konjac fibers exhibited a great digestion regulation potential. Our findings provide valuable references for the development of dietary fiber-based satiety-enhancing functional foods.

Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals.

AIMS/INTRODUCTION: Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features. MATERIALS AND METHODS: Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals. RESULTS: We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33-1.69, P < 0.001; OR 1.31, 95% CI 1.04-1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C-peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11-1.80, P = 0.006) and lower fasting C-peptide for LADA (OR 1.55, 95% CI 1.01-2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C-peptide or glutamic acid decarboxylase antibody positivity. CONCLUSIONS: The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes.