Assessment of the Safety and Exopolysaccharide Synthesis Capabilities of Bacillus amyloliquefaciens D189 Based on Complete Genome and Phenotype Analysis.

Exopolysaccharides (EPS) are natural macromolecular carbohydrates with good functional activity and physiological activities, which can be utilized as an emulsifier, viscosity enhancer, stabilizer, gelling agent, and water retention agent in a wide range of food products. In this study, the whole genome of Bacillus amyloliquefaciens D189, an EPS-producing bacteria, was sequenced. The result showed that D189 contains a single, circular chromosome of 3,963,356 bp with an average GC content of 45.74% and 3996 coding genes. The gene annotation results showed that D189 is a potentially safe strain and confirmed to be safe associated with hemolytic assay, and antibiotic resistance test. Meanwhile, D189 genome possessed 240 genes related to carbohydrate metabolism. More importantly, D189 could transport 9 sugars and contained a complete biosynthetic pathway for 8 nucleotide sugars. Based on the validation experiments, strain D189 could metabolize 8 sugars (glucose, sucrose, trehalose, fructose, cellobiose, maltose, mannitol, and N-acetyl-D-glucosamine) to produce EPS, with the highest yield of 1.212 g/L when sucrose was the carbon source. Therefore, the whole genome sequencing preliminarily elucidated the physiological mechanism of EPS, providing several pathways for engineering D189 to further enhance the yield of EPS.

Tuning collective anion motion enables superionic conductivity in solid-state halide electrolytes.

Halides of the family Li3MX6 (M = Y, In, Sc and so on, X = halogen) are emerging solid electrolyte materials for all-solid-state Li-ion batteries. They show greater chemical stability and wider electrochemical stability windows than existing sulfide solid electrolytes, but have lower room-temperature ionic conductivities. Here we report the discovery that the superionic transition in Li3YCl6 is triggered by the collective motion of anions, as evidenced by synchrotron X-ray and neutron scattering characterizations and ab initio molecular dynamics simulations. Based on this finding, we used a rational design strategy to lower the transition temperature and thus improve the room-temperature ionic conductivity of this family of compounds. We accordingly synthesized Li3YClxBr6-x and Li3GdCl3Br3 and achieved very high room-temperature conductivities of 6.1 and 11 mS cm-1 for Li3YCl4.5Br1.5 and Li3GdCl3Br3, respectively. These findings open new routes to the design of room-temperature superionic conductors for high-performance solid batteries.

Association between gestational hypnotic benzodiazepine receptor agonists exposure and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: Hypnotic benzodiazepine receptor agonists (HBRA) are frequently prescribed in pregnancy but little is known about their effects on pregnancy outcomes. Herein, we systematically reviewed the evidence on the effects of HBRA exposure during pregnancy and risk of preterm birth (PTB), small for gestational age (SGA), birth defects, and low birth weight (LBW). METHODS: We reviewed the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science from the earliest possible date to 17th May 2024 and included all studies examining adverse pregnancy outcomes with gestational exposure to HBRA. RESULTS: Nine studies were included. Meta-analysis showed that HBRA exposure led to a significant increase in the risk of PTB (OR: 1.28 95% CI: 1.05, 1.56 I2 = 73%), SGA (OR: 1.24 95% CI: 1.18, 1.30 I2 = 0%), and LBW (OR: 1.51 95% CI: 1.27, 1.78 I2 = 26%). We noted no significant association between HBRA exposure in pregnancy and subsequent birth defects (OR: 0.90 95% CI: 0.63, 1.28 I2 = 56%). Subgroup analysis based on exposure time, type of HBRA, method of assessment of exposure, control of psychiatric diagnosis, and psychotropic drugs altered the results of PTB and SGA but not for birth defects. CONCLUSION: HBRA exposure during pregnancy may lead to a small but significant increase in the risk of PTB, SGA, and LBW. HBRA is not associated with an increased risk of birth defects. There are several limitations of current evidence especially with regards to adjustment for psychiatric illness and co-mediations which need to be overcome by future studies.

Habitual use of glucosamine and adverse liver outcomes among patients with type 2 diabetes and MASLD.

BACKGROUND: Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant-inflammation effect. OBJECTIVE: This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non-users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. METHODS: Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio-metabolic risk factors, excluding patients with moderate to severe alcohol consumption. RESULTS: During a mean follow-up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09-1.69) as well as most individual MALOs except for ascites. The multivariable-adjusted HRs of MALOs within 3, 5 and 10 years among non-users of glucosamine compared with regular users were 1.79 (95% CI .69-2.03), 1.88 (95% CI 1.21-2.54) and 1.32 (95% CI 1.05-1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self-reports to diagnose diabetes confirmed the findings. CONCLUSIONS: The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD.

Severe dawn phenomenon predicts long-term risk of all-cause mortality in patients with type 2 diabetes.

AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.

Halide Heterogeneous Structure Boosting Ionic Diffusion and High-Voltage Stability of Sodium Superionic Conductors.

The development of solid-state sodium-ion batteries (SSSBs) heavily hinges on the development of an superionic Na+ conductor (SSC) that features high conductivity, (electro)chemical stability, and deformability. The construction of heterogeneous structures offers a promising approach to comprehensively enhancing these properties in a way that differs from traditional structural optimization. Here, this work exploits the structural variance between high- and low-coordination halide frameworks to develop a new class of halide heterogeneous structure electrolytes (HSEs). The halide HSEs incorporating a UCl3 -type high-coordination framework and amorphous low-coordination phase achieves the highest Na+ conductivity (2.7 mS cm-1 at room temperature, RT) among halide SSCs so far. By discerning the individual contribution of the crystalline bulk, amorphous region, and interface, this work unravels the synergistic ion conduction within halide HSEs and provides a comprehensive explanation of the amorphization effect. More importantly, the excellent deformability, high-voltage stability, and expandability of HSEs enable effective SSSB integration. Using a cold-pressed cathode electrode composite of uncoated Na0.85 Mn0.5 Ni0.4 Fe0.1 O2 and HSEs, the SSSBs present stable cycle performance with a capacity retention of 91.0% after 100 cycles at 0.2 C.

Glycemic variability: Measurement, target, impact on complications of diabetes and does it really matter?

Over the past two decades, there has been continuous advancement in the accuracy and complexity of continuous glucose monitoring devices. Continuous glucose monitoring provides valuable insights into blood glucose dynamics, and can record glucose fluctuations accurately and completely. Glycemic variability (GV) is a straightforward measure of the extent to which a patient's blood glucose levels fluctuate between high peaks and low nadirs. Many studies have investigated the relationship between GV and complications, primarily in the context of type 2 diabetes. Nevertheless, the exact contribution of GV to the development of diabetes complications remains unclear. In this literature review, we aimed to summarize the existing evidence regarding the measurement, target level, pathophysiological mechanisms relating GV and tissue damage, and population-based studies of GV and diabetes complications. Additionally, we introduce novel methods for measuring GV, and discuss several unresolved issues of GV. In the future, more longitudinal studies and trials are required to confirm the exact role of GV in the development of diabetes complications.

Design principles for sodium superionic conductors.

Motivated by the high-performance solid-state lithium batteries enabled by lithium superionic conductors, sodium superionic conductor materials have great potential to empower sodium batteries with high energy, low cost, and sustainability. A critical challenge lies in designing and discovering sodium superionic conductors with high ionic conductivities to enable the development of solid-state sodium batteries. Here, by studying the structures and diffusion mechanisms of Li-ion versus Na-ion conducting solids, we reveal the structural feature of face-sharing high-coordination sites for fast sodium-ion conductors. By applying this feature as a design principle, we discover a number of Na-ion conductors in oxides, sulfides, and halides. Notably, we discover a chloride-based family of Na-ion conductors NaxMyCl6 (M = La-Sm) with UCl3-type structure and experimentally validate with the highest reported ionic conductivity. Our findings not only pave the way for the future development of sodium-ion conductors for sodium batteries, but also consolidate design principles of fast ion-conducting materials for a variety of energy applications.

Lithium-compatible and air-stable vacancy-rich Li9N2Cl3 for high-areal capacity, long-cycling all-solid-state lithium metal batteries.

Attaining substantial areal capacity (>3 mAh/cm2) and extended cycle longevity in all-solid-state lithium metal batteries necessitates the implementation of solid-state electrolytes (SSEs) capable of withstanding elevated critical current densities and capacities. In this study, we report a high-performing vacancy-rich Li9N2Cl3 SSE demonstrating excellent lithium compatibility and atmospheric stability and enabling high-areal capacity, long-lasting all-solid-state lithium metal batteries. The Li9N2Cl3 facilitates efficient lithium-ion transport due to its disordered lattice structure and presence of vacancies. Notably, it resists dendrite formation at 10 mA/cm2 and 10 mAh/cm2 due to its intrinsic lithium metal stability. Furthermore, it exhibits robust dry-air stability. Incorporating this SSE in Ni-rich LiNi0.83Co0.11Mn0.06O2 cathode-based all-solid-state batteries, we achieve substantial cycling stability (90.35% capacity retention over 1500 cycles at 0.5 C) and high areal capacity (4.8 mAh/cm2 in pouch cells). These findings pave the way for lithium metal batteries to meet electric vehicle performance demands.

Lithium crystallization at solid interfaces.

Understanding the electrochemical deposition of metal anodes is critical for high-energy rechargeable batteries, among which solid-state lithium metal batteries have attracted extensive interest. A long-standing open question is how electrochemically deposited lithium-ions at the interfaces with the solid-electrolytes crystalize into lithium metal. Here, using large-scale molecular dynamics simulations, we study and reveal the atomistic pathways and energy barriers of lithium crystallization at the solid interfaces. In contrast to the conventional understanding, lithium crystallization takes multi-step pathways mediated by interfacial lithium atoms with disordered and random-closed-packed configurations as intermediate steps, which give rise to the energy barrier of crystallization. This understanding of multi-step crystallization pathways extends the applicability of Ostwald's step rule to interfacial atom states, and enables a rational strategy for lower-barrier crystallization by promoting favorable interfacial atom states as intermediate steps through interfacial engineering. Our findings open rationally guided avenues of interfacial engineering for facilitating the crystallization in metal electrodes for solid-state batteries and can be generally applicable for fast crystal growth.

Understanding the Polymorphism of Cobalt Nanoparticles Formed in Electrodeposition-An In Situ XRD Study.

An advanced synchrotron-based in situ X-ray diffraction (XRD) technique is successfully developed and employed to track and monitor the formation and phase selection of cobalt (Co) in electrodeposition in real time and verify DFT computational results. The impacts of a number of controlling factors including the pH of the electrolyte and deposition overpotential are systematically studied. The results show that the yielded phase of the electrodeposited Co is controlled by both thermodynamics and kinetics. The low pH low overpotential condition favors the formation of the thermodynamically stable fcc phase. While the high pH high overpotential condition promotes the formation of the metastable hcp phase. The experimental results agree well with the nanometric phase diagram computed with DFT. Layer-by-layer alternative stacking of fcc-hcp polymorphic phases can be facilely fabricated by just varying the overpotential. This work not only offers an effective means to control the phase of electroplating of Co but also presents a new approach to reveal the fundamental insights of the formation of metals under electrochemical reduction driving force.

Frustration in Super-Ionic Conductors Unraveled by the Density of Atomistic States.

The frustration in super-ionic conductors enables their exceptionally high ionic conductivities, which are desired for many technological applications including batteries and fuel cells. A key challenge in the study of frustration is the difficulties in analyzing a large number of disordered atomistic configurations. Using lithium super-ionic conductors as model systems, we propose and demonstrate the density of atomistic states (DOAS) analytics to quantitatively characterize the onset and degree of disordering, reveal the energetics of local disorder, and elucidate how the frustration enhances diffusion through the broadening and overlapping of the energy levels of atomistic states. Furthermore, material design strategies aided by the DOAS are devised and demonstrated for new super-ionic conductors. The DOAS is generally applicable analytics for unraveling fundamental mechanisms in complex atomistic systems and guiding material design.

Superionic Conducting Halide Frameworks Enabled by Interface-Bonded Halides.

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl6]x- octahedra and generate a tetrahedron-assisted Li+ ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl3, for example, in which 1-dimensional channels are enclosed by [SmCl9]6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li+ ion hopping. The fast Li+ diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10-4 S cm-1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl3/halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation.

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects ß-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study.

AIMS: To investigate the association between short-term glycemic variability (GV) and all-cause mortality in type 2 diabetes with well-controlled glucose profile by continuous glucose monitoring (CGM). METHODS: In this prospective study, 1839 diabetes patients who reached percentage of time in the target glucose range of 3.9-10 mmol/L > 70%, percentage of time above range of 10 mmol/L < 25% and percentage of time below range of 3.9 mmol/L < 4% on CGM were enrolled and were classified into five groups by coefficient of variation for glucose (%CV) level: ≤20%, 20-25%, 25-30%, 30-35%, and > 35%. Cox proportional hazard models were used to estimate hazard ratios (HRs) of all-cause mortality risk associated with the different %CV categories. RESULTS: At baseline, participants had mean age of 60.9 years and mean HbA1c of 7.3% (56 mmol/mol). A total of 165 deaths were identified during a median follow-up of 6.9 years. In multivariate Cox regression analysis, HRs associated with %CV categories were 1.00, 1.16 (95% CI 0.78-1.73), 1.38 (95% CI 0.89-2.15), 1.33 (95% CI 0.77-2.29) and 2.26 (95% CI 1.13-4.52) for all-cause mortality. CONCLUSIONS: Greater %CV was associated with increased risk for all-cause mortality even among patients with seemingly well-controlled glucose status.

Multi-principal elemental intermetallic nanoparticles synthesized via a disorder-to-order transition.

Nanoscale multi-principal element intermetallics (MPEIs) may provide a broad and tunable compositional space of active, high-surface area materials with potential applications such as catalysis and magnetics. However, MPEI nanoparticles are challenging to fabricate because of the tendency of the particles to grow/agglomerate or phase-separated during annealing. Here, we demonstrate a disorder-to-order phase transition approach that enables the synthesis of ultrasmall (4 to 5 nm) and stable MPEI nanoparticles (up to eight elements). We apply just 5 min of Joule heating to promote the phase transition of the nanoparticles into L10 intermetallic structure, which is then preserved by rapidly cooling. This disorder-to-order transition results in phase-stable nanoscale MPEIs with compositions (e.g., PtPdAuFeCoNiCuSn), which have not been previously attained by traditional synthetic methods. This synthesis strategy offers a new paradigm for developing previously unexplored MPEI nanoparticles by accessing a nanoscale-size regime and novel compositions with potentially broad applications.

The Effectiveness of Traditional Chinese Medicine Jinlida Granules on Glycemic Variability in Newly Diagnosed Type 2 Diabetes: A Double-Blinded, Randomized Trial.

This study aimed to evaluate the influence of Jinlida granules on glycemic variability with or without metformin treatment in patients with newly diagnosed type 2 diabetes. This study was a 16-week, double-blinded, randomized, controlled clinical trial. The enrolled patients with newly diagnosed type 2 diabetes were randomly divided into four groups: control, Jinlida, metformin, and combination treatment groups. A retrospective continuous glucose monitoring (CGM) system was used for subcutaneous interstitial glucose monitoring for 3 days consecutively. Hemoglobin A1c (HbA1c), traditional Chinese medicine symptom score, and CGM parameters, including glucose coefficient of variation, standard deviation of blood glucose values, and time in range of glucose 3.9-10.0 mmol/L, were assessed pre-test and post-test. A total of 138 participants completed the entire procedure. Compared with the pre-test, fasting plasma glucose, 2 hour postprandial plasma glucose, HbA1c, and traditional Chinese medicine symptom score all decreased in the four groups at the end of the test, and the combination treatment group showed the most significant decrease. In terms of CGM parameters, time in range of the Jinlida and metformin groups improved after intervention compared with the baseline (Jinlida group: 78.68 ± 26.15 versus 55.47 ± 33.29; metformin group: 87.29 ± 12.21 vs. 75.44 ± 25.42; P < 0.01). Additionally, only the Jinlida group showed decreased glucose standard deviation after intervention (1.57 ± 0.61 vs. 1.96 ± 0.95; P < 0.01). Jinlida granules can improve glycemic control and glycemic variability in patients with newly diagnosed type 2 diabetes. Clinical trial registration number: ChiCTR-IOR-16009296.

Interfacial Defect of Lithium Metal in Solid-State Batteries.

All-solid-state battery with Li metal anode is a promising rechargeable battery technology with high energy density and improved safety. Currently, the application of Li metal anode is plagued by the failure at the interfaces between lithium metal and solid electrolyte (SE). However, little is known about the defects at Li-SE interfaces and their effects on Li cycling, impeding further improvement of Li metal anodes. Herein, by performing large-scale atomistic modeling of Li metal interfaces with common SEs, we discover that lithium metal forms an interfacial defect layer of nanometer-thin disordered lithium at the Li-SE interfaces. This interfacial defect Li layer is highly detrimental, leading to interfacial failure such as pore formation and contact loss during Li stripping. By systematically studying and comparing incoherent, coherent, and semi-coherent Li-SE interfaces, we find that the interface with good lattice coherence has reduced Li defects at the interface and has suppressed interfacial failure during Li cycling. Our finding discovered the critical roles of atomistic lithium defects at interfaces for the interfacial failure of Li metal anode, and motivates future atomistic-level interfacial engineering for Li metal anode in solid-state batteries.

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial.

Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n = 22) and an exercise group (EX, n = 23). The subjects either adopted LCD (carbohydrate intake < 50 g/day) or performed moderate-to-vigorous exercise (⩾ 30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX ( - 3.56 ± 0.37 kg vs. - 1.24 ± 0.39 kg, P < 0.001), as well as a larger reduction in fat mass ( - 2.10 ± 0.18 kg vs. - 1.25 ± 0.24 kg, P = 0.007) and waist circumference ( - 5.25 ± 0.52 cm vs. - 3.45 ± 0.38 cm, P = 0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.