Leisure Activity, Childhood Starvation, and Risk of Incident Diabetes in Older Adults: Evidence From a Chinese Nationwide Cohort Study.

OBJECTIVE: This study explores the impact of leisure activity and the association between childhood starvation and the risk of diabetes in older Chinese adults. DESIGN: Prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort study in China. SETTING AND PARTICIPANTS: A total of 4637 older adults aged ≥65 years, all with documented diabetes history, experiences of childhood starvation, and participation in leisure activities were recruited. METHODS: Childhood starvation exposure was assessed via self-reported responses from a structured questionnaire. The leisure activities were measured by 9 distinctive components and categorized into 3 distinct categories: productive activity, recreational activity, and sedentary activity. Diabetes status was determined by self-reported, physician-diagnosed cases during the follow-up period. Nonparametric survival models were employed for analysis. RESULTS: Over an average follow-up period of 4.3 years, 215 of 4637 participants (4.6%) reported a confirmed diagnosis of diabetes. Nonparametric survival models showed that those reporting childhood starvation had a higher risk of late-life diabetes [hazard ratio (HR) 1.72, 95% CI 1.21-2.44]. Engaging in productive activity (HR 0.90, 95% CI 0.83-0.99) and recreational activity (HR 0.88, 95% CI 0.77-1.00) was linked with a reduced risk of late-life diabetes. Sedentary activity did not show a significant effect. Further analysis highlighted the interactions effects of leisure activities on diabetes risk across different demographic and historical exposure subgroups. CONCLUSIONS AND IMPLICATIONS: Engaging in productive and recreational leisure activities was inversely associated with the risk of diabetes in older adults who experienced childhood starvation. Promoting such activities could be beneficial in mitigating long-term diabetes risk related to early-life nutritional deficiencies.

Dietary patterns interfere with gut microbiota to combat obesity.

Obesity and obesity-related metabolic disorders are global epidemics that occur when there is chronic energy intake exceeding energy expenditure. Growing evidence suggests that healthy dietary patterns not only decrease the risk of obesity but also influence the composition and function of the gut microbiota. Numerous studies manifest that the development of obesity is associated with gut microbiota. One promising supplementation strategy is modulating gut microbiota composition by dietary patterns to combat obesity. In this review, we discuss the changes of gut microbiota in obesity and obesity-related metabolic disorders, with a particular emphasis on the impact of dietary components on gut microbiota and how common food patterns can intervene in gut microbiota to prevent obesity. While there is promise in intervening with the gut microbiota to combat obesity through the regulation of dietary patterns, numerous key questions remain unanswered. In this review, we critically review the associations between dietary patterns, gut microbes, and obesity, aiming to contribute to the further development and application of dietary patterns against obesity in humans.

Efficient Adsorption and Elimination of Tm3+ For Enhanced Seed Germination Using Pillar[5]Arene Polymer.

While rare earth elements (REEs) are essential for modern technology, their production methods raise concerns for agriculture. Researchers are now exploring ways to control and recycle REEs pollution, aiming to minimize agricultural impacts and potentially even develop methods to utilize these elements for improved crop yields. Regarding this issue, a new type of pillar[5]arene polymer (Pol-P[5]-BTZP) has been designed and synthesized by click reaction to enhance the efficiency of adsorption and recovery of rare earth metals. This polymer incorporates the unique structure of 2,6-di-1,2,3-triazolyl-pyridine. The results of various analyses revealed that Pol-P[5]-BTZP exhibits excellent thermal stability, a high specific surface area, and well-distributed networks of micropores and mesoporous structures. The adsorption capacity of Pol-P[5]-BTZP for Tm3+, a representative REE, was evaluated using the Langmuir and Freundlich isothermal adsorption models with a maximum adsorption capacity (Qmax) of 127.71 mg/g. Furthermore, the versatility of Pol-P[5]-BTZP in adsorption and recovering various REEs was tested. In addition to its adsorption capabilities, the potential of Pol-P[5]-BTZP for rare earth recovery and reuse was assessed through experiments on the impact of Tm3+ and La3+ on seed germination. These experiments demonstrated the wide-ranging applicability of Pol-P[5]-BTZP in recovering and reusing REEs for green agriculture.

The Role of Ubiquitination and the E3 Ligase Nedd4 in Regulating Corneal Epithelial Wound Healing.

Purpose: Ubiquitination serves as a fundamental post-translational modification in numerous cellular events. Yet, its role in regulating corneal epithelial wound healing (CEWH) remains elusive. This study endeavored to determine the function and mechanism of ubiquitination in CEWH. Methods: Western blot and immunoprecipitation were used to discern ubiquitination alterations during CEWH in mice. Interventions, including neuronally expressed developmentally downregulated 4 (Nedd4) siRNA and proteasome/lysosome inhibitor, assessed their impact on CEWH. In vitro analyses, such as the scratch wound assay, MTS assay, and EdU staining, were conducted to gauge cell migration and proliferation in human corneal epithelial cells (HCECs). Moreover, transfection of miR-30/200 coupled with a luciferase activity assay ascertained their regulatory mechanism on Nedd4. Results: Global ubiquitination levels were markedly increased during the mouse CEWH. Importantly, the application of either proteasomal or lysosomal inhibitors notably impeded the healing process both in vivo and in vitro. Furthermore, Nedd4 was identified as an essential E3 ligase for CEWH. Nedd4 expression was significantly upregulated during CEWH. In vivo studies revealed that downregulation of Nedd4 substantially delayed CEWH, whereas further investigations underscored its role in regulating cell proliferation and migration, through the Stat3 pathway by targeting phosphatase and tensin homolog (PTEN). Notably, our findings pinpointed miR-30/200 family members as direct regulators of Nedd4. Conclusions: Ubiquitination holds pivotal significance in orchestrating CEWH. The critical E3 ligase Nedd4, under the regulatory purview of miR-30 and miR-200, facilitates CEWH through PTEN-mediated Stat3 signaling. This revelation sheds light on a prospective therapeutic target within the realm of CEWH.

The "4+4" Medical Education Pilot Program at PUMC: Implementation, Performance, and Prospects.

Peking Union Medical College (PUMC) launched the "4+4" Clinical Medicine Pilot Class in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" clinical medical pilot program at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "medicine + x" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

Structural Phase Separation of Membranes and Fibers.

Lipid membranes interact with protein filaments on a superstructural level such that they may colocalize or spatially segregate in a living cell, whereas higher-order organization of membranes and fibers is less well explored in artificial systems. Herein, we report on the structural separation of a dispersed, membranous phase and a continuous, fibrous phase in a synthetic system. Systematic characterization of its thermodynamics and kinetics uncovers a physical principle governing phase separation: Interlamellar repulsion, favoring expansion of the membranous phase, is balanced by fibrous network elasticity, preferring the opposite. A direct consequence of this principle is the spatial addressability of the phase separation, preferably localized to soft regions of the fibrous network. Guided by this principle, we design a fibrous network with different spatial heterogeneity to modulate the phase separation, realizing a "memory" effect, patterned separation, and gradient separation. The current spatially addressable phase separation is in great contrast to the conventional ones, in which nucleation is difficult to predict or control. The fact that the membranous and fibrous phases compete for space has implications for the intracellular interactions between endoplasmic reticulum membranes and cytoskeletal filaments.

MCM8 interacts with DDX5 to promote R-loop resolution.

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.

Risk factors for malnutrition in patients with diabetic foot ulcer and its association with prolonged length of hospitalization.

PURPOSE: The study was designed to investigate the occurrence and risk factors of malnutrition in diabetic foot ulcers (DFU) patients and examine the association between malnutrition and length of stay (LOS). METHODS: This observational study included DFU hospitalized patients in two campuses of a hospital from January 2021 to June 2023. The diagnosis standard of malnutrition was established by using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were followed up to ascertain the length of hospitalization, and hospital stays longer than 17 days were considered as prolonged LOS. To explore the risk factors of malnutrition and the association between malnutrition and LOS, univariate and multivariate logistic regression analyses were performed. RESULTS: Overall 219 DFU patients were enrolled, malnutrition was identified in 38.36% of patients according to GLIM criteria, and 92 patients (42%) were recognized as prolonged LOS. Logistic regression analyses showed that BMI (P <0.001), Alb (P = 0.002), HbA1c (P <0.001), ulcer infection (P <0.001), LOS (P = 0.010), and ABI (P = 0.024) were independent risk factors for malnutrition. Besides, malnutrition by GLIM criteria was closely related to prolonged LOS and malnourished DFU patients were 2.857 times (95% CI, 1.497-5.450; P = 0.001) likely to present prolonged LOS than that of normal nutrition. CONCLUSION: Malnutrition was considered to be extremely prevalent in DFU patients and was associated with approximately three times higher likelihood of prolonged LOS. Implementing and disseminating the diagnostic criteria during routine practice is crucial, given the predictive efficacy of GLIM criteria.

Causes of Corneal Melt After the Boston Keratoprosthesis Type I: The Chinese People's Liberation Army General Hospital Experience.

PURPOSE: The purpose of this study was to evaluate the long-term incidence, risk factors, and the management of corneal melt following Boston type I keratoprosthesis (B-KPro I) implantation. METHODS: This is a retrospective observational case series. Data were collected regarding demographics, preoperative characteristics, incidence, and outcomes of corneal melt in 102 patients who underwent B-KPro I in the Chinese PLA General Hospital between 2011 and 2018, with a follow-up period ranging from 4 to 11 years. RESULTS: Chemical burn was the most common indication for B-KPro I (n = 56; 53.8%), followed by ocular trauma (n = 26; 25.0%). During the follow-up period (107 ± 25.7 months), corneal melt occurred in 60 cases among 37 eyes (35.6%), with an incidence of 20.2% at 1 year after surgery. Fourteen cases presented with recurrent corneal melt. Patients with multiple corneal allograft failures had a higher risk of corneal melt. Thermal burns, compared with alkali burns, significantly elevated the odds ratio (OR) of corneal melt (OR, 5.11; 95% confidence interval, 1.05-24.86; P = 0.043). CONCLUSIONS: Corneal melt significantly reduced the retention time of KPro ( P < 0.01), and its coexistence with other complications further shortened the retention time. A specific pattern of corneal melt occurrence was identified, with a peak incidence at 1 year postoperatively. Our findings suggest variations in the risk of corneal melt among different indications, with thermal burns carrying the highest OR. Moreover, each previous failed keratoplasty doubled the risk of corneal melt after B-KPro I.

A Comprehensive Study on Implant Stability Quotient (ISQ) in View of Resonance Frequency and Spectrum Analysis.

PURPOSE: This experimental study investigated how well implant stability quotient (ISQ) represents resonance frequency. Benchtop experiments on standardized samples, mimicking a premolar section of a mandible, were conducted to correlate an ISQ value and a resonance frequency to synthetic bone density and an incremental insertion torque. A frequency spectrum analysis was performed to check the validity of the resonance frequency analysis (RFA). MATERIALS AND METHODS: Branemark Mk III implants with dimensions ∅4 Å~ 11.5 mm were placed in Sawbones test models of five different densities (40, 30, 40/20, 20, 15 PCF). An incremental insertion torque was recorded during implant placement. To perform stability measurements, the test models were clamped partially in a vise (unclamped volume 10 Å~ 20 Å~ 34 mm). A MultiPeg was attached onto the implants, and a Penguin RFA measured ISQ. Simultaneously, motion of the MultiPeg was monitored via a laser Doppler vibrometer and processed by a spectrum analyzer to obtain the resonance frequency. Tightness of the clamp was adjusted to vary the resonance frequency. A statistical analysis produced a linear correlation coefficient 𝑅 among the measured ISQ, resonance frequency, and incremental insertion torque. RESULTS: The resonance frequency had high correlation to the incremental insertion torque (𝑅 = 0.978), confirming the validity of using RFA for this study. Measured ISQ data were scattered and had low correlation to the resonance frequency (𝑅 = 0.214) as well as the incremental insertion torque (𝑅 = -0.386). The spectrum analysis revealed simultaneous presence of multiple resonance frequencies. CONCLUSIONS: For the designed benchtop tests, resonance frequency does indicate implant stability in view of Sawbones density and incremental insertion torque. ISQ measurements, however, do not correlate well to the resonance frequency, and may not reflect the stability when multiple resonance frequencies are present simultaneously.

Recent Advances of Food Hazard Detection Based on Artificial Nanochannel Sensors.

Food quality and safety are related to the health and safety of people, and food hazards are important influencing factors affecting food safety. It is strongly necessary to develop food safety rapid detection technology to ensure food safety. As a new detection technology, artificial nanochannel-based electrochemical and other methods have the advantages of being real-time, simple, and sensitive and are widely used in the detection of food hazards. In this paper, we review artificial nanochannel sensors as a new detection technology in food safety for different types of food hazards: biological hazards (bacteria, toxins, viruses) and chemical hazards (heavy metals, organic pollutants, food additives). At the same time, we critically discuss the advantages and disadvantages of artificial nanochannel sensor detection, as well as the restrictions and solutions of detection, and finally look forward to the challenges and development prospects of food safety detection technology based on the limitations of artificial nanochannel detection. We expect to provide a theoretical basis and inspiration for the development of rapid real-time detection technology for food hazards and the production of portable detection equipment in the future.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Recent Advances in Stimulus-Responsive Nanocarriers for Pesticide Delivery.

In an effort to make pesticide use safer, more efficient, and sustainable, micro-/nanocarriers are increasingly being utilized in agriculture to deliver pesticide-active agents, thereby reducing quantities and improving effectiveness. In the use of nanopesticides, the choice to further design and prepare pesticide stimulus-responsive nanocarriers based on changes in the plant growth environment (light, temperature, pH, enzymes, etc.) has received more and more attention from researchers. Based on this, this paper examines recent advancements in nanomaterials for the design of stimulus-responsive micro-/nanocarriers. It delves into the intricacies of preparation methods, material enhancements, in vivo/ex vivo controlled release, and application techniques for controlled release formulations. The aim is to provide a crucial reference for harnessing nanotechnology to pursue reduced pesticide use and increased efficiency.

Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Case report: unprecedented case of infantile cerebral infarction following COVID-19 and favorable outcome.

The 2019 novel coronavirus, SARS-CoV-2, was highly prevalent in China as of December 2022, causing a range of symptoms, predominantly affecting the respiratory tract. While SARS-CoV-2 infection in children is generally mild, severe cases, especially in infants, are rare. We present a case of a previously healthy 7-month-old infant who developed cerebral infarction and coagulation dysfunction three days after COVID-19 onset. Clinically, the infant had weakness in the left limbs and pinpoint bleeding spots. A cranial magnetic resonance imaging showed ischemic strokes in the right basal ganglia and thalamus. Laboratory tests indicated thrombocytopenia and coagulation dysfunction. Inflammatory cytokines like interleukin-10 were elevated, with increased CD3+, CD4+, and CD8+ T lymphocytes but decreased CD3- CD16+ CD56+ natural killer cells. Treatment included mannitol, dexamethasone, oral aspirin, and vitamins B1 and B6 for reducing intracranial pressure, antiinflammation, anticoagulation, and nerve support, respectively. During the recovery phase, rehabilitation therapy focused on strength training, fine motor skills, and massage therapy. The infant gradually improved and successfully recovered. While rare, such cases can lead to severe complications. These combined efforts were instrumental in achieving significant functional recovery in the patient, demonstrating that even in severe instances of pediatric cerebral infarction due to COVID-19, positive outcomes are attainable with early and comprehensive medical response.

Acute kidney injury during autologous stem cell transplantation in light chain amyloidosis with kidney involvement and their impact on prognosis.

Acute kidney injury (AKI) is a complication related to important organ dysfunction during autologous stem cell transplantation (ASCT) in light chain (AL) amyloidosis. This study aims to validate the risk factors of AKI during different periods of ASCT and the impact of AKI on long-term outcomes. 302 patients with AL amyloidosis and kidney involvement who underwent ASCT were included. The procedures from stem cell mobilization to 30 days after transplantation were categorized into four periods: Period 0 (stem cell mobilization and harvest), Period 1 (preparation), Period 2 (conditioning and transplantation), and Period 3 (engraftment). The incidence of AKI during ASCT was 27.15% (0.66% in Period 0, 6.62% in Period 1, 15.23% in Period 2, and 6.95% in Period 3). The major causes of AKI were capillary leak syndrome in Period 0, ganciclovir or sulfamethoxazole/trimethoprim in Period 1, high-dose melphalan in Period 2, and engraftment syndrome in Period 3. AKI in different periods had distinct risk factors and predictive models. AKI was a risk factor for both kidney survival and overall survival (OS). Even recovered AKI reduced 10-year kidney survival from 91.7% to 68.4% (p = 0.002) and 10-year OS from 91.1% to 77.7% (p = 0.005).

The inhibition of MARCO by PolyG alleviates pulmonary fibrosis via regulating mitochondrial function in a silicotic rat model.

Silicon dioxide (SiO2)-induced pulmonary fibrosis is potentially associated with the impairment of mitochondrial function. Previous research found that inhibition of macrophage receptor with collagenous structure (MARCO) could alleviate particle-induced lung injury by regulating phagocytosis and mitigating mitochondrial damage. The present study aims to explore the underlying anti-fibrosis mechanism of polyguanylic acid (PolyG, MARCO inhibitor) in a silicotic rat model. Hematoxylin and eosin and Masson staining were performed to visualize lung tissue pathological changes. Confocal microscopy, transmission electron microscope, western blot analysis, quantitative real-time PCR (qPCR), and adenosine triphosphate (ATP) content assay were performed to evaluate collagen content, mitochondrial function, and morphology changes in SiO2-induced rat pulmonary fibrosis. The results suggested that SiO2 exposure contributed to reactive oxygen species aggregation and the reduction of respiratory complexes and ATP synthesis. PolyG treatment could effectively reduce MARCO expression and ameliorate lung injury and fibrosis by rectifying the imbalance of mitochondrial respiration and energy synthesis. Furthermore, PolyG could maintain mitochondrial homeostasis by promoting peroxisome proliferator-activated receptor-coactivator 1 α (PGC1α)-mediated mitochondrial biogenesis and regulating fusion and fission. Together, PolyG could ameliorate SiO2-induced pulmonary fibrosis via inhibiting MARCO to protect mitochondrial function.

Organic-Hydrochloride-Modified ZnO Electron Transport Layer for Efficient Defect Passivation and Stress Release in Rigid and Flexible all Inorganic Perovskite Solar Cells.

All inorganic CsPbI2Br perovskite (AIP) has attracted great attention due to its excellent resistance against thermal stress as well as the remarkable capability to deliver high-voltage output. However, CsPbI2Br perovskite solar cells (PeSCs) still encounter critical challenges in attaining both high efficiency and mechanical stability for commercial applications. In this work, formamidine disulfide dihydrochloride (FADD) modified ZnO electron transport layer (ETL) has been developed for fabricating inverted devices on either rigid or flexible substrate. It is found that the FADD modification leads to efficient defects passivation, thereby significantly reducing charge recombination at the AIP/ETL interface. As a result, rigid PeSCs (r-PeSCs) deliver an enhanced efficiency of 16.05% and improved long-term thermal stability. Moreover, the introduced FADD can regulate the Young's modulus (or Derjaguin-Muller-Toporov (DMT) modilus) of ZnO ETL and dissipate stress concentration at the AIP/ETL interface, effectively restraining the crack generation and improving the mechanical stability of PeSCs. The flexible PeSCs (f-PeSCs) exhibit one of the best performances so far reported with excellent stability against 6000 bending cycles at a curvature radius of 5 mm. This work thus provides an effective strategy to simultaneously improve the photovoltaic performance and mechanical stability.

Dipterocarpoidae genomics reveal their demography and adaptations to Asian rainforests.

Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Global, neuronal or ß cell-specific deletion of inceptor improves glucose homeostasis in male mice with diet-induced obesity.

Insulin resistance is an early complication of diet-induced obesity (DIO)1, potentially leading to hyperglycaemia and hyperinsulinaemia, accompanied by adaptive ß cell hypertrophy and development of type 2 diabetes2. Insulin not only signals via the insulin receptor (INSR), but also promotes ß cell survival, growth and function via the insulin-like growth factor 1 receptor (IGF1R)3-6. We recently identified the insulin inhibitory receptor (inceptor) as the key mediator of IGF1R and INSR desensitization7. But, although ß cell-specific loss of inceptor improves ß cell function in lean mice7, it warrants clarification whether inceptor signal inhibition also improves glycaemia under conditions of obesity. We assessed the glucometabolic effects of targeted inceptor deletion in either the brain or the pancreatic ß cells under conditions of DIO in male mice. In the present study, we show that global and neuronal deletion of inceptor, as well as its adult-onset deletion in the ß cells, improves glucose homeostasis by enhancing ß cell health and function. Moreover, we demonstrate that inceptor-mediated improvement in glucose control does not depend on inceptor function in agouti-related protein-expressing or pro-opiomelanocortin neurons. Our data demonstrate that inceptor inhibition improves glucose homeostasis in mice with DIO, hence corroborating that inceptor is a crucial regulator of INSR and IGF1R signalling.