Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB.

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.

Effects of aging and diabetes on the deformation mechanisms and molecular structural characteristics of collagen fibrils under daily activity.

Crosslinking plays an important role in collagen-based tissues since it affects mechanical behavior and tissue metabolism. Aging and diabetes affect the type and density of crosslinking, effectively altering tissue properties. However, most studies focus on these effects under large stress rather than daily activities. We focus on the deformation mechanisms and structural change at the binding sites for integrins, proteoglycans, and collagenase in collagen fibrils using a fully atomistic model. We show that high-connectivity enzymatic crosslinking (our "HC" model, representing normal tissues) and advanced-glycation end-products (our "Glucosepane" model, which increase in diabetes) result in uniform deformation under daily activity, but low-connectivity enzymatic crosslinking (our "LC" model, representing aging tissues) does not. In particular, the HC model displays more sliding, which may explain the ability of healthy tissues to absorb more strain energy. In contrast, AGEs induce instability in the structures near the binding sites, which would affect the tissue metabolism of the collagen molecule. Our results provide important insights into the molecular mechanisms of collagen and a possible explanation for the role of crosslinking in tissues undergoing daily activity.

Effects of the Degree of Phenol Substitution on Molecular Structures and Properties of Chitosan-Phenol-Based Self-Healing Hydrogels.

Click chemistry is commonly used to prepare hydrogels, and chitosan-phenol prepared by using a Schiff base has been widely employed in the field of biomaterials. Chitosan-phenol is a derivative of chitosan; the phenol groups can disrupt both the inter- and intramolecular hydrogen bonds in chitosan, thereby reducing its crystallinity and improving its water solubility. In addition, chitosan-phenol exhibits various beneficial physiological functions. However, it is still unclear whether the degree of phenol substitution in the chitosan main chain affects the molecular interactions and structural properties of the self-healing hydrogels. To explore this issue, we investigated the molecular structure and network of self-healing hydrogels composed of chitosan-phenol with varying degrees of phenol substitution and dibenzaldehyde poly(ethylene oxide) (DB-PEO) using molecular dynamics simulations. We observed that when the degree of phenol substitution in the self-healing hydrogel was less than 15%, an increase in the degree of phenol substitution led to an increase in the interactions between chitosan-phenol and DB-PEO, and it enhanced the dynamic covalent bond cross-linking generated through the Schiff base reaction. However, when the degree of phenol substitution exceeded 15%, excessive phenol groups caused excessive intramolecular interactions within chitosan-phenol molecules, which reduced the binding between chitosan-phenol and DB-PEO. Our results revealed the influence of the degree of phenol substitution on the molecular structure of the self-healing hydrogels and showed an optimal degree of phenol substitution. These findings provide important insights for the future design of self-healing hydrogels based on chitosan and should help in enhancing the applicability of hydrogels in the field of biomedicine.

In-plane gate graphene transistor with epitaxially grown molybdenum disulfide passivation layers.

We demonstrate in-plane gate transistors based on the molybdenum disulfide (MoS2)/graphene hetero-structure. The graphene works as channels while MoS2 functions as passivation layers. The weak hysteresis of the device suggests that the MoS2 layer can effectively passivate the graphene channel. The characteristics of devices with and without removal of MoS2 between electrodes and graphene are also compared. The device with direct electrode/graphene contact shows a reduced contact resistance, increased drain current, and enhanced field-effect mobility. The higher field-effect mobility than that obtained through Hall measurement indicates that more carriers are present in the channel, rendering it more conductive.

Molecular interactions of tannic acid and matrix metalloproteinases 2 and 9.

Tannic acid (TA) has antibacterial, antioxidant, and anti-inflammatory properties and acts as an adhesive, hemostatic, and crosslinking agent in hydrogels. Matrix metalloproteinases (MMPs), a family of endopeptidase enzymes, play important roles in tissue remodeling and wound healing. TA has been reported to inhibit MMP-2/- 9 activities, thereby improving both tissue remodeling and wound healing. However, the mechanism of interaction of TA with MMP-2 and MMP-9 has not been fully elucidated. In this study, the full atomistic modeling approach was applied to explore the mechanisms and structures of TA binding with MMP-2 and MMP-9. Macromolecular models of the TA-MMP-2/- 9 complex were built by docking based on experimentally resolved MMP structures, and further equilibrium processes were examined by molecular dynamics (MD) simulations to investigate the binding mechanism and structural dynamics of the TA-MMP-2/- 9 complexes. The molecular interactions between TA and MMPs, including H-bond formation and hydrophobic and electrostatic interactions, were analyzed and decoupled to elucidate the dominant factors in TA-MMP binding. TA binds to MMPs mainly at two binding regions, residues 163-164 and 220-223 in MMP-2 and residues 179-190 and 228-248 in MMP-9. Two arms of TA participate in binding MMP-2 with 3.61 hydrogen bonds. On the other hand, TA binds MMP-9 with a distinct configuration involving four arms with 4.75 hydrogen bonds, resulting in a tighter binding conformation. Understanding the binding mechanism and structural dynamics of TA with these two MMPs provides crucial and fundamental knowledge regarding the inhibitory and stabilizing effects of TA on MMPs.

Persistent charge storage and memory operation of top-gate transistors solely based on two-dimensional molybdenum disulfide.

We fabricate top-gate transistors on the three-layer molybdenum disulfide (MoS2) with three, two, and one layers in the source and drain regions using atomic layer etching (ALE). In the presence of ALE, the device at zero gate voltage can exhibit high and low levels of drain current under the forward and reverse gate bias, respectively. The hysteresis loop on the transfer curve of transistor indicates that two distinct charge states exist in the device within a range of gate bias. A long retention time of the charge is observed. Unlike conventional semiconductor memories with transistors and capacitors, the two-dimensional (2D) material itself plays two parts in the current conduction and charge storage. The persistent charge storage and memory operation of the multilayer MoS2transistors with thicknesses of a few atomic layer will further expand the device application of 2D materials with reduced linewidths.

Unraveling the molecular mechanism of collagen flexibility during physiological warmup using molecular dynamics simulation and machine learning.

Physiological warmup plays an important role in reducing the injury risk in different sports. In response to the associated temperature increase, the muscle and tendon soften and become easily stretched. In this study, we focused on type I collagen, the main component of the Achilles tendon, to unveil the molecular mechanism of collagen flexibility upon slight heating and to develop a model to predict the strain of collagen sequences. We used molecular dynamics approaches to simulate the molecular structures and mechanical behavior of the gap and overlap regions in type I collagen at 307 K, 310 K, and 313 K. The results showed that the molecular model in the overlap region is more sensitive to temperature increases. Upon increasing the temperature by 3 degrees Celsius, the end-to-end distance and Young's modulus of the overlap region decreased by 5% and 29.4%, respectively. The overlap region became more flexible than the gap region at higher temperatures. GAP-GPA and GNK-GSK triplets are critical for providing molecular flexibility upon heating. A machine learning model developed from the molecular dynamics simulation results showed good performance in predicting the strain of collagen sequences at a physiological warmup temperature. The strain-predictive model could be applied to future collagen designs to obtain desirable temperature-dependent mechanical properties.

Revisional One Anastomosis Gastric Bypass (OAGB) for Poor Response of Duodenal-Jejunal Bypass with Sleeve Gastrectomy (DJB-SG) (Video Report).

BACKGROUND: Bariatric surgery has actually focused not only on obesity but also more on the improvements or remission of the metabolic diseases. Therefore, revisional surgery is indicated for patients with poor response to the primary bariatric surgery to control weight and obesity-associated medical conditions. METHOD: In this video report, the patient was a 27-year-old Asian female with an initial BMI of 36.5 kg/m2 and poorly controlled type 2 diabetes (HbA1c: 11.9%). She underwent primary bariatric surgery of laparoscopic duodenal-jejunal bypass with sleeve gastrectomy (DJB-SG) in June 2019. She had a nadir BMI of 28.8 kg/m2 (corresponding body weight of 72 kg) in June 2020. However, she regained weight (BMI: 34 kg/m2) and had a relapse of diabetes with an HbA1c of 12.0% at the time of consultation for revisional bariatric surgery (RBS) in September 2022. After a multidisciplinary team evaluation, laparoscopic procedures of one anastomosis gastric bypass (OAGB) with resizing the gastric tube, removal of duodenal-jejunal anastomosis, and lengthening of the biliopancreatic limb were performed. RESULTS: The operative time was 186 min and blood loss was 50 ml. There were no intraoperative or postoperative complications. The patient had an uneventful postoperative course and was discharged on postoperative day 5. At the 3-month follow-up after RBS, the patient had lost 13 kg (weight dropped from 85 to 72 kg) and achieve remission of diabetes with HbA1c of 5.7%. CONCLUSION: Laparoscopic OAGB is technically feasible and practical as a revisional procedure for poor response of DJB-SG.

From Our One Anastomosis Gastric Bypass (OAGB) Experience to Establishing Single Anastomosis Sleeve Ileal (SASI) Bypass Procedure: A Single-Center Report.

BACKGROUND: Bariatric surgery has been proven to be the most effective treatment for obesity with or without metabolic syndrome. One anastomosis gastric bypass (OAGB) is a well-established bariatric procedure developed over the past 20 years with excellent outcomes. Single anastomosis sleeve ileal (SASI) bypass is introduced as a novel bariatric and metabolic procedure. There is some similarity between these two operations. This study aimed to present our SASI procedure based on the past experience of the OAGB in our center. METHOD: Thirty patients with obesity underwent SASI surgery from March 2021 to June 2022. Herein, we demonstrated our techniques step by step and key points of techniques learned from our experience with OAGB (shown in the video) with satisfying surgical outcomes. The clinical characteristics, peri-operative variables, and short-term outcomes were reviewed. RESULTS: There was no case of conversion to open surgery. The mean operative time, volume of blood loss, and hospital stay were 135.2 ± 39.2 min, 16.5 ± 6.2 mL, and 3.6 ± 0.8 days, respectively. There is no postoperative leakage, bleeding, or mortality. The percentage of total weight loss and excess weight loss at 6 months were 31.2 ± 6.5 and 75.3 ± 14.9, respectively. Improvement in type 2 diabetes (11/11, 100%), hypertension (14/26, 53.8%), dyslipidemia (16/21, 76.2%), and obstructive sleep apnea (9/11, 81.8%) were observed at 6 months after surgery. CONCLUSION: Our experience showed that our proposed SASI technique is feasible and may help surgeons perform this promising bariatric procedure without encountering many obstacles.

Mechanical and Crack Propagating Behavior of Sierpinski Carpet Composites.

Fractals, mathematically defined as "self-similar subsets at different scales", are ubiquitous in nature despite their complexity in assembly and formulation. Fractal geometry formed by simple components has long been applied to many fields, from physics and chemistry to electronics and architecture. The Sierpinski carpet (SC), a fractal with a Hausdorff dimension of approximately 1.8933, has two-dimensional space-filling abilities and therefore provides many structural applications. However, few studies have investigated its mechanical properties and fracture behaviors. Here, utilizing the lattice spring model (LSM), we constructed SC composites with two base materials and simulated tensile tests to show how fractal iterations affect their mechanical properties and crack propagation. From observing the stress-strain responses, we find that, for either the soft-base or stiff-base SC composites, the second iteration has the optimal mechanical performance in the terms of stiffness, strength, and toughness compared to the composites with higher hierarchies. The reason behind this surprising result is that the largest stress intensities occur at the corners of the smallest squares in the middle zone, which consequently induces crack nucleation. We also find that the main crack tends to deflect locally in SC composites with a soft matrix, but in global main crack behavior, SC composites with a stiff matrix have a large equivalent crack deflection. Furthermore, considering the inherent anisotropy of SC composites, we rotated the samples by 45°. The results show that the tensile strength and toughness of rotated SC composites are inferior and the crack propagating behaviors are distinct from the standard SC composites. This finding infers advanced engineering for crack control and deflection by adjusting the orientation of SC composites. Overall, our study opens the door for future engineering applications in stretchable devices, seismic metamaterials, and structural materials with tunable properties and hierarchies.

Design and Simulation of InGaN-Based Red Vertical-Cavity Surface-Emitting Lasers.

We propose a highly polarized vertical-cavity surface-emitting laser (VCSEL) consisting of staggered InGaN multiple quantum wells (MQWs), with the resonance cavity and polarization enabled by a bottom nanoporous (NP) n-GaN distributed Bragg reflectors (DBRs), and top TiO2 high-index contrast gratings (HCGs). Optoelectronic simulations of the 612 nm VCSEL were systematically and numerically investigated. First, we investigated the influences of the NP DBR and HCG geometries on the optical reflectivity. Our results indicate that when there are more than 17 pairs of NP GaN DBRs with 60% air voids, the reflectance can be higher than 99.7%. Furthermore, the zeroth-order reflectivity decreases rapidly when the HCG's period exceeds 518 nm. The optimal ratios of width-to-period (52.86 ± 1.5%) and height-to-period (35.35 ± 0.14%) were identified. The staggered MQW design also resulted in a relatively small blue shift of 5.44 nm in the emission wavelength under a high driving current. Lastly, we investigated the cavity mode wavelength and optical threshold gain of the VCSEL with a finite size of HCG. A large threshold gain difference of approximately 67.4-74% between the 0th and 1st order transverse modes can be obtained. The simulation results in this work provide a guideline for designing red VCSELs with high brightness and efficiency.

Deep Learning for Detecting Supraspinatus Calcific Tendinopathy on Ultrasound Images.

Background: The aim of the study was to evaluate the feasibility of convolutional neural network (CNN)-based deep learning (DL) algorithms to dichotomize shoulder ultrasound (US) images with or without supraspinatus calcific tendinopathy (SSCT). Methods: This was a retrospective study pertaining to US examinations that had been performed by 18 physiatrists with 3-20 years of experience. 133,619 US images from 7836 consecutive patients who had undergone shoulder US examinations between January 2017 and June 2019 were collected. Only images with longitudinal or transverse views of supraspinatus tendons (SSTs) were included. During the labeling process, two physiatrists with 6-and 10-year experience in musculoskeletal US independently classified the images as with or without SSCT. DenseNet-121, a pre-trained model in CNN, was used to develop a computer-aided system to identify US images of SSTs with and without calcifications. Testing accuracy, sensitivity, and specificity calculated from the confusion matrix was used to evaluate the models. Results: A total of 2462 images were used for developing the DL algorithm. The longitudinal-transverse model developed with a CNN-based DL algorithm was better for the diagnosis of SSCT when compared with the longitudinal and transverse models (accuracy: 91.32%, sensitivity: 87.89%, and specificity: 94.74%). Conclusion: The developed DL model as a computer-aided system can assist physicians in diagnosing SSCT during the US examination.

The age factor influencing long-term physical functionality in stroke patients undergoing intra-arterial thrombectomy treatment.

The treatment of acute ischemic stroke is heavily time-dependent, and even though, with the most efficient treatment, the long-term functional outcome is still highly variable. In this current study, the authors selected acute ischemic stroke patients who were qualified for intravenous thrombolysis with recombinant tissue plasminogen activator and followed by intra-arterial thrombectomy. With primary outcome defined by the functional level in a 1-year follow-up, we hypothesize that patients with older age are at a disadvantage in post-stroke recovery. However, an age-threshold should be determined to help clinicians in selection of patients to undergo such therapy. This is a retrospective chart review study that include 92 stroke patients in Changhua Christian hospital with a total of 68 evaluation indexes recorded. The current study utilized the forward stepwise regression model whose Adj-R2 and P value in search of important variables for outcome prediction. The chngpt package in R indicated the threshold point of the age factor directing the better future functionality of the stroke patients. Datasets revealed the threshold of the age set at 79 the most appropriate. Admission Barthel Index, Age, ipsilateral internal carotid artery resistance index (ICA RI), ipsilateral vertebral artery (VA) PI, contralateral middle cerebral artery (MCA) stenosis, contralateral external carotid artery (ECA) RI, and in-hospital pneumonia are the significant predicting variables. The higher the age, in-hospital pneumonia, contralateral MCA stenosis, ipsilateral ICA RI and ipsilateral VA PI, the less likely patient to recover from functional deficits as the result of acute ischemic stroke; the higher the value of contralateral ECA RI and admission Barthel Index, the better chance to full functional recovery at 1-year follow up. Parameters of pre-intervention datasets could provide important information to aid first-line clinicians in decision making. Especially, in patients whose age is above 79 receives diminish return in the benefit to undergo such intervention and should be considered seriously by both the patients and the physicians.

In situ tunable circular dichroism of flexible chiral metasurfaces composed of plasmonic nanorod trimers.

The circularly polarized light source is one of the keys to chiral photonic circuits and systems. However, it is difficult to integrate conventional light-emitting devices with circular polarization converters directly into compact chip-scale photonic systems partly because of their bulky structures. In this study, in situ optical chirality tunable nanorod trimer metasurfaces consisting of two types of nanorod dimers are demonstrated and integrated with a flexible polydimethylsiloxane (PDMS) substrate. The optical chirality variations originating from the tunable asymmetricity of nanorod trimers under different stretching scenarios are evaluated. Through the processes, the gap distances between nanorods are varied, and the degree of circular polarization of the transmitted wave is controlled through the manipulation of localized surface plasmon resonance (LSPR) coupling. The results reveal the circular dichroism tunability and durability of fabricated chiral metasurfaces which can be important elements for chip-scale flexible optoelectronic integrated circuits for sensing, display and communication applications.

Performance Analyses of Photonic-Crystal Surface-Emitting Laser: Toward High-Speed Optical Communication.

This study conducts comprehensive performance analyses of a commercial photonic-crystal surface-emitting laser (PCSEL) via small-signal measurement and the bit-error-rate test. Meanwhile, the radio frequency characteristics of the PCSEL are unveiled for the first time. Compared to the vertical-cavity surface-emitting lasers, the PCSEL shows great potential for a broader optical bandwidth that is benefited from the high optical-confinement factor. A maximum bandwidth of around 2.32 GHz is experimentally observed when the PCSEL was biased at 340 mA. Moreover, a theoretical calculation was applied to shed light on the characteristics of the small-signal measurement, providing a deep insight into the corresponding intrinsic response model. The signal transmission capability of the PCSEL was investigated as well. The maximum bit rate and corresponding rise time transmitted at 500 Mbps are 1.2 Gbps and 186.16 ps, respectively. Thus, a high-speed PCSEL can be realised with a shrunk form factor, serving as a promising candidate for the next-generation light sources in high-speed optical communication.

Optogenetic manipulation of cell migration with high spatiotemporal resolution using lattice lightsheet microscopy.

Lattice lightsheet microscopy (LLSM) featuring three-dimensional recording is improved to manipulate cellular behavior with subcellular resolution through optogenetic activation (optoLLSM). A position-controllable Bessel beam as a stimulation source is integrated into the LLSM to achieve spatiotemporal photoactivation by changing the spatial light modulator (SLM) patterns. Unlike the point-scanning in a confocal microscope, the lattice beams are capable of wide-field optical sectioning for optogenetic activation along the Bessel beam path.We show that the energy power required for optogenetic activations is lower than 1 nW (or 24 mWcm-2) for time-lapses of CRY2olig clustering proteins, and membrane ruffling can be induced at different locations within a cell with subcellular resolution through light-triggered recruitment of phosphoinositide 3-kinase. Moreover, with the epidermal growth factor receptor (EGFR) fused with CRY2olig, we are able to demonstrate guided cell migration using optogenetic stimulation for up to 6 h, where 463 imaging volumes are collected, without noticeable cellular damages.

Predicting pullout strength of pedicle screws in broken bones from X-ray images.

Pedicle screw fixation is one of the most common procedures used in spinal fusion surgery. The screw loosening is a major concern, which may be caused by broken pedicles. In vitro pullout tests or insertion torque are the main approaches for assessing the stability of the screw; however, direct evidence was lacking for clinical human spines. Here, we aim to provide a model that can predict the pullout strengths of pedicle screws in various pedicle conditions from X-ray images. A weighted embedded bone volume (EBV) model is proposed for pullout strengths prediction by considering the bone heterogeneity and confinement of the screw. We showed that the pullout strength is proportional to the EBV for homogeneous bone and the weighted EBV for layered composite bone. The proposed weighted EBV model is validated with in vitro Sawbones® pullout experiments. The results show that the model has better accuracy than the simple EBV model, with a coefficient of determination of 0.94. The proposed weighted EBV model can help assess the stability of a pedicle screw in a broken pedicle by simply examining 2D X-ray images.

Molecular interaction mechanisms of glycol chitosan self-healing hydrogel as a drug delivery system for gemcitabine and doxorubicin.

Glycol chitosan is a derivative of chitosan that has attracted attention in recent years due to its biocompatibility and biodegradability. Due to its unique biological characteristics, it has been widely used in hydrogels and biomaterials. In this study, we explored the loading efficiency of a self-healing hydrogel (GC-DP) comprising glycol chitosan (GC) and telechelic difunctional poly(ethylene glycol) (DF-PEG) for delivering the anticancer drugs gemcitabine and doxorubicin through full atomistic simulations. We also constructed full atomistic models of the two drug delivery systems at three drug concentrations of 10%, 40%, and 80% to understand how the drug concentration affects the loading efficiency and molecular structure of the GC-DP hydrogels. Through the analysis of the results, we show that the GC-DP hydrogel exhibits excellent loading efficiency for both gemcitabine and doxorubicin at all drug concentrations (10%, 40% and 80%). Our results reveal that the main mechanism of interaction between the GC-DP hydrogels and gemcitabine is van der Waals adsorption and that the dominant interactions between the GC-DP hydrogel and doxorubicin are hydrogen bonds for the D10 model and van der Waals adsorption for the D40 and D80 models. Our results provide molecular insights into how drug molecules are carried by hydrogel materials and indicate that the GC-DP hydrogel is a promising candidate for carrying both gemcitabine and doxorubicin, and thus serving as a novel drug carrier for cancer treatment.

Computational insights into the substrate recognition mechanism of cartilage extracellular matrix degradation.

Articular cartilage is connective tissue that forms a slippery load-bearing joint surface between bones. With outstanding mechanical properties, it plays an essential role in cushioning impact and protecting the ends of bones. Abnormal mechanical stimulation, such as repetitive overloading or chondral injury, induces excessive cartilage extracellular matrix (ECM) degradation, leading to osteoarthritis and other joint disorders. A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) is an aggrecanase that dominates the catalysis of aggrecan, the major proteoglycan in the cartilage ECM. Intriguingly, unlike its critical cleavage site Glu373-374Ala, another potential cleavage site, Glu419-420Ala, composed of the same amino acids in the aggrecan interglobular domain, is not a major cleavage site. It remains unclear how ADAMTS-5 distinguishes between them and hydrolyzes the correct scissile bonds. This research introduces a bottom-up in silico approach to reveal the molecular mechanism by which ADAMTS-5 recognizes the cleavage site on aggrecan. It is hypothesized that the sequence in the vicinity assists ADAMTS-5 in positioning the cleavage site. Specific residues were found to serve as binding sites, helping aggrecan bind more stably and fit into the enzyme better. The findings provide insight into the substrate binding and recognition mechanism for cartilage ECM degradation from a brand new atomic-scale perspective, laying the foundation for prophylaxis and treatment of related joint diseases.