Diversities of Mechanism in Patients with VHL Syndrome and diabetes: A Report of Two Cases and Literature Review.

Background: Von Hippel-Lindau (VHL) syndrome is characterized by tumorous lesions affecting multiple organs. Pancreatic involvement in VHL syndrome can present as endocrine tumors and pancreatic cysts, which can interfere with both exocrine and endocrine functions of the pancreas. Diabetes is an uncommon complication of VHL syndrome. Purpose: This study aims to summarize the various mechanisms of diabetes in VHL syndrome by reporting two cases and conducting a literature review. Methods: We analyzed the clinical and imaging data of two patients with VHL syndrome and diabetes. Additionally, we reviewed the existing literature to explore the clinical diversities and management strategies for VHL syndrome complicated with diabetes. Results: The first patient presented with liver metastasis of pancreatic neuroendocrine tumor and multiple pheochromocytoma. After surgery, the patient's diabetic control improved, as evidenced by a significant reduction in insulin dosage. This indicates a potential insulin resistance due to elevated metanephrine levels prior to surgery and partial insulin deficiency caused by distal pancreatectomy. The second patient had multiple hemangioblastomas, as well as multiple pancreatic cysts and positive pancreatic islet autoantibodies. Diabetes in this case may be attributed to pancreatic lesions and the coexistence of autoimmune insulitis. A literature review of other patients with VHL combined with diabetes revealed multiple mechanisms, including increased catecholamine levels, pancreatic lesions, surgical removal of pancreatic tissue, endocrine treatment, and possibly the coexistence of autoimmune insulitis. Conclusion: VHL syndrome complicated with diabetes involves diverse mechanisms.

Thin-film lithium niobate electro-optic isolator fabricated by photolithography assisted chemo-mechanical etching.

We report an electro-optic isolator fabricated on thin-film lithium niobate by photolithography-assisted chemo-mechanical etching that shows an isolation of 39.50 dB and an overall fiber-to-fiber loss of 2.6 dB.

A Bioinspired Gradient Design Strategy for Cellulose-Based Electromagnetic Wave Absorbing Structural Materials.

Cellulose nanofiber (CNF) possesses excellent intrinsic properties, and many CNF-based high-performance structural and functional materials have been developed recently. However, the coordination of the mechanical properties and functionality is still a considerable challenge. Here, a CNF-based structural material is developed by a bioinspired gradient structure design using hollow magnetite nanoparticles and the phosphorylation-modified CNF as building blocks, which simultaneously achieves a superior mechanical performance and electromagnetic wave absorption (EMA) ability. Benefiting from the gradient design, the flexural strength of the structural material reached ∼205 MPa. Meanwhile, gradient design improves impedance matching, contributing to the high EMA ability (-59.5 dB) and wide effective absorption width (5.20 GHz). Besides, a low coefficient of thermal expansion and stable storage modulus was demonstrated as the temperature changes. The excellent mechanical, thermal, and EMA performance exhibited great potential for application in stealth equipment and electromagnetic interference protecting electronic packaging materials.

Tough and Moldable Sustainable Cellulose-Based Structural Materials via Multiscale Interface Engineering.

All-natural materials derived from cellulose nanofibers (CNFs) are expected to be used to replace engineering plastics and have attracted much attention. However, the lack of crack extension resistance and 3D formability of nanofiber-based structural materials hinders their practical applications. Here, a multiscale interface engineering strategy is reported to construct high-performance cellulose-based materials. The sisal microfibers are surface treated to expose abundant active CNFs with positive charges, thereby enhancing their interfacial combination with the negatively charged CNFs. The robust multiscale dual network enables easy molding of multiscale cellulose-based structural materials into complex 3D special-shaped structures, resulting in nearly twofold and fivefold improvements in toughness and impact resistance compared with those of CNFs-based materials. Moreover, this multiscale interface engineering strategy endows cellulose-based structural materials with better comprehensive performance than petrochemical-based plastics and broadens cellulose's potential for lightweight applications as structural materials with lower environmental effects.

Pituitary stalk interruption syndrome and liver cirrhosis associated with diabetes and an inactivating KCNJ11 gene mutation: a case report and literature review.

Background: Pituitary stalk interruption syndrome (PSIS) is a congenital disease commonly found in patients with combined pituitary hormone deficiency (CPHD). Most PSIS patients manifest growth retardation and delayed puberty. We report a rare case of PSIS with tall stature, liver cirrhosis and diabetes, possibly caused by an inactivating KCNJ11 gene mutation. Case presentation: A 37-year-old female patient initially presented with liver cirrhosis and diabetes, without any secondary sexual characteristics. Endocrine investigation indicated CPHD. Small anterior pituitary, invisible pituitary stalk and no eutopic posterior lobe hypersignal in the sella turcica viewed in magnetic resonance imaging (MRI) confirmed the diagnosis of PSIS. Despite receiving no growth hormone or sex hormone therapy, she reached a final height of 186 cm. Liver histopathology revealed nonalcoholic fatty cirrhosis. Genetic testing identified a heterozygous p.Arg301Cys mutation in the KCNJ11 gene. Conclusion: This is a rare case of PSIS with liver cirrhosis and diabetes associated with an inactivating KCNJ11 gene mutation. It's supposed that early hyperinsulinism caused by the KCNJ11 gene mutation, as well as delayed epiphyseal closure due to estrogen deficiency, contributed to the patient's exceptionally tall stature. Untreated growth hormone deficiency (GHD) resulted in increased visceral fat, leading to nonalcoholic fatty liver disease (NAFLD) and cirrhosis. The decline in ß cell function with age, combined with NAFLD, may have played a role in the development of diabetes.

On-chip coherent beam combination of waveguide amplifiers on Er3+-doped thin film lithium niobate.

We demonstrate on-chip coherent beam combination of two waveguide amplifiers on Er3+-doped thin film lithium niobate (Er:TFLN) platform. Our device is built based on an electro-optic modulator fabricated on Er:TFLN. The output power of the coherently combined amplifiers is measured as high as 12.9 mW, surpassing that of previous single waveguide amplifiers based on an Er3+-doped thin film lithium niobate platform.

[Advances in the preclinical and clinical research of proteolysis targeting chimera].

Proteolysis targeting chimera (PROTAC) refers to heterobifunctional small molecules that can simultaneously bind an E3 ubiquitin ligase and a target protein, enabling specific degradation of the target protein with the aid of the ubiquitin proteasome system. At present, most PROTAC drugs are in the clinical trial stage, and the ligands are mainly non-covalent compounds. PROTAC drugs have the advantage of overcoming drug resistance and degrading "undruggable" target proteins, but non-covalent ligands could lead to the hook effect that undermines drug efficacy. With its own advantages, covalent ligands can avoid the occurrence of this phenomenon, which is of great help to the development of PROTAC. This review summarizes the progress in preclinical and clinical research and application of PROTAC molecules targeting three different classes of protein targets, including intranuclear, transmembrane, and cytosolic proteins. We also offer perspective discussions to provide research ideas and references for the future development of PROTAC.

Decreased programmed cell death ligand 2-positive monocytic myeloid-derived suppressor cells and programmed cell death protein 1-positive T-regulatory cells in patients with type 2 diabetes: implications for immunopathogenesis.

Objectives: The activation of immune cells plays a significant role in the progression of type 2 diabetes. This study aimed to investigate the potential role of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) in type 2 diabetes. Methods: A total of 61 patients diagnosed with type 2 diabetes were recruited. Clinical characteristics were reviewed and peripheral blood samples were collected. We calculated the percentage of different cells. Frequencies of MDSC subsets refered to the percentage of G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DR-/low) in CD45 positive cells and the percentage of M-MDSCs (CD14+CD15-CD11b+CD33+HLA-DR-/low) in lymphocytes plus monocytes. Results: Frequencies of programmed cell death ligand 1-positive granulocytic MDSCs (PD-L1+ G-MDSCs), programmed cell death ligand 2-positive monocytic MDSCs (PD-L2+ M-MDSCs), PD-L2+ G-MDSC, and programmed cell death protein 1-positive Tregs (PD-1+Tregs) were decreased in patients with type 2 diabetes. The frequency of PD-1+ Tregs was positively related to PD-L2+ M-MDSCs (r= 0.357, P = 0.009) and negatively related to HbA1c (r = -0.265, P = 0.042), fasting insulin level (r = -0.260, P = 0.047), and waist circumference (r = -0.373, P = 0.005). Conclusions: Decreased PD-L2+ M-MDSCs and PD-1+ Tregs may promote effector T cell activation, leading to chronic low-grade inflammation in type 2 diabetes. These findings highlight the contribution of MDSCs and Tregs to the immunopathogenesis of type 2 diabetes and suggest their potential as targets for new therapeutic approaches.

Electro-optically tunable optical delay line with a continuous tuning range of ∼220 fs in thin-film lithium niobate.

We demonstrate fabrication of a 30-cm-long thin-film lithium niobate (TFLN) optical delay line (ODL) incorporated with segmented microelectrodes of 24-cm total length using the femtosecond laser lithography technique. The transmission spectra of the unbalanced Mach-Zehnder interferometers (MZIs) reveal an ultra-low propagation loss of 0.025 dB/cm. The device exhibits a low half-wave voltage of 0.45 V, corresponding to a voltage-length product of 10.8 V·cm, which is equivalent to 5.4 V·cm in the push-pull configuration. We also demonstrate a high electro-optic (EO) tuning efficiency of 3.146 fs/V and a continuous tuning range of 220 fs in the fabricated ODL.

The concordance and discordance of diabetic kidney disease and retinopathy in patients with type 2 diabetes mellitus: A cross-sectional study of 26,809 patients from 5 primary hospitals in China.

Introduction: Diabetic kidney disease (DKD) and diabetic retinopathy (DR) share similar pathophysiological mechanisms. However, signs of DKD may be present at diagnosis of diabetes without retinopathy. Risk factors for the development of DKD and DR may not be identical. Methods: This study aimed to evaluate the concordance and discordance between DKD and DR by investigating the distribution of DKD and DR in patients with type 2 diabetes mellitus from 5 Chinese cities. A total of 26,809 patients were involved in this study. The clinical characteristics were compared among patients based on the presence of DKD and DR. Logistic regression models were used to analyze the independent risk factors of DKD and DR. Results: The prevalence of DKD and DR was 32.3% and 34.6%, respectively. Among eligible patients, 1,752 patients without DR had an increased urinary albumin-to-creatinine ratio (ACR) or reduced estimated glomerular filtration rate (eGFR), and 1,483 patients with DR had no DKD. The positive predictive value of DR for DKD was 47.4% and negative predictive value was 67.1%. Elder age, male gender, a longer duration of disease, higher values of waist circumference and HbA1c were associated with both DR and DKD. A lower educational level was associated with DR. Higher BP and TG would predict increased prevalence of DKD. Conclusions: DKD and DR shared many risk factors, but a significant discordance was present in patients with type 2 diabetes mellitus. DKD was more strongly associated with blood pressure and triglycerides than DR.

Nacre-Inspired Bacterial Cellulose/Mica Nanopaper with Excellent Mechanical and Electrical Insulating Properties by Biosynthesis.

The exploration of extreme environments has become necessary for understanding and changing nature. However, the development of functional materials suitable for extreme conditions is still insufficient. Herein, a kind of nacre-inspired bacterial cellulose (BC)/synthetic mica (S-Mica) nanopaper with excellent mechanical and electrical insulating properties that has excellent tolerance to extreme conditions is reported. Benefited from the nacre-inspired structure and the 3D network of BC, the nanopaper exhibits excellent mechanical properties, including high tensile strength (375 MPa), outstanding foldability, and bending fatigue resistance. In addition, S-Mica arranged in layers endows the nanopaper with remarkable dielectric strength (145.7 kV mm-1 ) and ultralong corona resistance life. Moreover, the nanopaper is highly resistant to alternating high and low temperatures, UV light, and atomic oxygen, making it an ideal candidate for extreme environment-resistant materials.

An All-Natural Wood-Inspired Aerogel.

The oriented pore structure of wood endows it with a variety of outstanding properties, among which the low thermal conductivity has attracted researchers to develop wood-like aerogels as excellent thermal insulation materials. However, the increasing demands of environmental protection have put forward new and strict requirements for the sustainability of aerogels. Here, we report an all-natural wood-inspired aerogel consisting of all-natural ingredients and develop a method to activate the surface-inert wood particles to construct the aerogel. The obtained wood-inspired aerogel has channel structure similar to that of natural wood, endowing it with superior thermal insulation properties to most existing commercial sponges. In addition, remarkable fire retardancy and complete biodegradability are integrated. With the above outstanding performances, this sustainable wood-inspired aerogel will be an ideal substitute for the existing commercial thermal insulation materials.

Ultrastrong, Thermally Stable, and Food-Safe Seaweed-Based Structural Material for Tableware.

Widely used disposable plastic tableware is usually buried or directly discharged into the natural environment after using, which poses potential threats to the natural environment and human health. To solve this problem, nondegradable plastic tableware needs to be replaced by tableware composed of biodegradable structural materials with both food safety and the excellent mechanical and thermal properties. Here, a food-safe sargassum cellulose nanofiber (SCNF) is extracted from common seaweed in an efficient and low energy consuming way under mild reaction conditions. Then, by assembling the SCNF into a dense bulk material, a strong sargassum cellulose nanofiber structural material (SCNSM) with high strength (283 MPa) and high thermal stability (>160 °C) can be prepared. The SCNSM also possesses good machinability, which can be processed into tableware with different shapes, e.g., knives and forks. The overall performance of the SCNSM-based tableware is better than commercial plastic, wood-based, and poly(lactic acid) tableware, which shows great application potential in the tableware field.

Simultaneous spatial and temporal focusing optical vortex pulses for micromachining through optically transparent materials.

We introduce the optical vortex beam into simultaneous spatial and temporal focusing (SSTF) technique, and theoretically and experimentally demonstrate the local control of peak intensity distribution at the focus of a simultaneous spatiotemporally focused optical vortex (SSTF OV) beam. To avoid nonlinear self-focusing in the conventional focusing scheme, a spatiotemporally focused femtosecond laser vortex beam was employed to achieve doughnut-shaped ablation and high aspect ratio (∼28) microchannels on the back surface of 3 mm thick soda-lime glass and fused silica substrates.

Manufacture of Three-Dimensional Optofluidic Spot-Size Converters in Fused Silica Using Hybrid Laser Microfabrication.

We propose a hybrid laser microfabrication approach for the manufacture of three-dimensional (3D) optofluidic spot-size converters in fused silica glass by a combination of femtosecond (fs) laser microfabrication and carbon dioxide laser irradiation. Spatially shaped fs laser-assisted chemical etching was first performed to form 3D hollow microchannels in glass, which were composed of embedded straight channels, tapered channels, and vertical channels connected to the glass surface. Then, carbon dioxide laser-induced thermal reflow was carried out for the internal polishing of the whole microchannels and sealing parts of the vertical channels. Finally, 3D optofluidic spot-size converters (SSC) were formed by filling a liquid-core waveguide solution into laser-polished microchannels. With a fabricated SSC structure, the mode spot size of the optofluidic waveguide was expanded from ~8 µm to ~23 µm with a conversion efficiency of ~84.1%. Further measurement of the waveguide-to-waveguide coupling devices in the glass showed that the total insertion loss of two symmetric SSC structures through two ~50 µm-diameter coupling ports was ~6.73 dB at 1310 nm, which was only about half that of non-SSC structures with diameters of ~9 µm at the same coupling distance. The proposed approach holds great potential for developing novel 3D fluid-based photonic devices for mode conversion, optical manipulation, and lab-on-a-chip sensing.

Euglycaemic Ketoacidosis Due to Extremely Low-Calorie Intake and Dehydration After Laparoscopic Sleeve Gastrectomy in a Patient with Type 2 Diabetes.

Background: Bariatric surgery is an effective therapy for type 2 diabetes mellitus (T2DM) and obesity. Euglycaemic ketoacidosis (EKA) has been reported in patients taking sodium-glucose cotransporter 2 (SGLT2) inhibitors after bariatric surgery. Cases of T2DM complicated with EKA without SGLT2 inhibitors after bariatric surgery are rarely reported. Purpose: To present a case report of a T2DM patient (without SGLT2 inhibitor use) who developed EKA soon after laparoscopic sleeve gastrectomy. Methods: Clinical records and interviews were used. Results: A 35-year-old female patient was diagnosed with T2DM and obesity. The patient underwent laparoscopic sleeve gastrectomy to lose weight and control her blood glucose levels. Her daily fluid intake was 800-1000 mL, and her daily caloric intake was less than 500 kcal during the first days after the surgery. She was prescribed degludec insulin, metformin and dulaglutide and her blood sugar was lower than 13.9 mmol/L. On postoperative Day 6, the patient complained of fatigue and vomiting. Blood gas analysis and urine analysis supported the diagnosis of ketoacidosis. Fluid resuscitation, insulin and glucose were administered to the patient immediately. On postoperative Day 8, the patient recovered without any symptoms. Conclusion: We report an extremely rare case of T2DM in which the patient developed EKA after laparoscopic sleeve gastrectomy owing to extremely low-calorie intake and dehydration. Physicians should be on alert for ketoacidosis in patients with T2DM after bariatric surgery with an euglycaemic status, even without the use of SGLT2 inhibitors or the presence of stresses, such as infection.Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Levetiracetam Attenuates the Spinal Cord Injury Induced by Acute Trauma via Suppressing the Expression of Perforin.

The spinal cord injury (SCI) is one of the major reasons causing the motor dysfunctions of the patients. At present, few therapeutic strategies can effectively improve the symptom of SCI. Levetiracetam has been confirmed to alleviate the injury of nerve cells, while its functions in SCI remains unclear. In this study, C57BL/6J mice were used to establish SCI models to observe the effect of levetiracetam on SCI. The mice were fed with 180 mg/kg levetiracetam when suffering from SCI, and Basso mouse score (BMS) and CatWalk-assisted gait analysis were used to observe the motor functions of the mice. Nissl staining and TUNEL staining were used to observe the injury of nerve cells. The abundance of inflammatory factors was measured by ELISA. The permeability of blood-spinal cord barrier (BSCB) in mice was detected with macrophage infiltration analysis. Moreover, the abundance of perforin in the tissues was detected by western blot. The results showed that the SCI mice treated with levetiracetam exhibited lighter motor dysfunction compared with the mice treated with saline. Levetiracetam can effectively reduce the inflammatory reactions and alleviate apoptosis of the nerve cells. Moreover, levetiracetam remarkably decreased the BSCB permeability of SCI mice. Besides, it was also found that levetiracetam can significantly inhibit the expression of perforin. In conclusion, this study suggests that levetiracetam can attenuate the injury of BSCB to block the progression of SCI via suppressing the expression of perforin.

Three-Dimensional Large-Scale Fused Silica Microfluidic Chips Enabled by Hybrid Laser Microfabrication for Continuous-Flow UV Photochemical Synthesis.

We demonstrate a hybrid laser microfabrication approach, which combines the technical merits of ultrafast laser-assisted chemical etching and carbon dioxide laser-induced in situ melting for centimeter-scale and bonding-free fabrication of 3D complex hollow microstructures in fused silica glass. With the developed approach, large-scale fused silica microfluidic chips with integrated 3D cascaded micromixing units can be reliably manufactured. High-performance on-chip mixing and continuous-flow photochemical synthesis under UV irradiation at ~280 nm were demonstrated using the manufactured chip, indicating a powerful capability for versatile fabrication of highly transparent all-glass microfluidic reactors for on-chip photochemical synthesis.