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Hsing-Ching Huang,1,* Liu-Ing Bih,1,* Ming-Miau Tsai,1 Tzu-Ling Chang,1 Wan-Chun Liao,1 Chung-Liang Lai2 1Department of Physical Medicine and Rehabilitation, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan; 2Department of Occupational Therapy, Asia University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chung-Liang Lai, Department of Occupational Therapy, Asia University, 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan, Email laipeter57@yahoo.com.twBackground: Traumatic brain injury (TBI) can result in functional impairments. Many patients with TBI require post-acute care to improve their functional skills and allow for greater self-independence and a better quality of life. Taiwan’s National Health Insurance proposed a nationwide post-acute care program in 2017 for patients with traumatic brain injury. The program’s goal was to maximize patients’ functional recovery and make it possible for them to return to their homes and communities. This study aimed to explore the effectiveness of such programs in Taiwan.Methods: This pilot study retrospectively evaluated a de-identified database that contained the scores of various assessments evaluated at admission and discharge. It used the data to determine the functional improvement of patients with traumatic brain injury after participating in post-acute care programs.Results: This study collected complete data from 27 patients. After an average of 45.11 days in the program, the patients showed significant improvement in the Barthel Activity Daily Living Index, the Lawton–Brody Instrumental Activity Daily Living Scale, the Mini Nutrition Assessment, the EuroQol Five Dimensions Questionnaire, the Berg Balance Scale, the Galveston Orientation and Amnesia Test, the Rancho Los Amigos Scale, the Concise Chinese Aphasia Test, and the Mini Mental State Examination. After discharge, 96% of the patients could return to their community.Conclusion: This pilot study concluded that the program significantly promoted functional recovery for patients and could help patients with traumatic brain injury return to their communities and reduce the risk of institutionalization. Thus, patients with the potential for functional recovery could receive post-acute care in regional or community hospitals immediately after being discharged from acute wards. In the future randomized controlled trials are needed to further confirm the clinical impact of this program.Keywords: traumatic brain injury, rehabilitation, post-acute care

Wei-Ching Huang,1,* Ming-Miau Tsai,1,* Tzu-Ling Chang,1 Chung-Liang Lai1,2 1Department of Physical Medicine and Rehabilitation, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan; 2Department of Occupational Therapy, Asia University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chung-Liang LaiDepartment of Physical Medicine and Rehabilitation, Taichung Hospital, Ministry of Health and Welfare, 199 San Min Road, Sec. 1, Taichung, Taiwan 403, TaiwanEmail laipeter57@yahoo.com.twBackground: Popliteal artery entrapment syndrome (PAES) is a rare disease in young adults and is thought to be under-diagnosed, and its main cause is the abnormal structure between the popliteal artery and gastrocnemius muscle. The patients experience symptoms after the blood vessels are compressed. Failure to diagnose and treat PAES can cause serious sequelae.Case: A 19-year-old male baseball pitcher with PAES type 2 suffered from left calf muscle tension and foot numbness and was mis-diagnosed for nearly a year. Finally, the lesion was detected by ultrasonography and confirmed by magnetic resonance imaging. After surgical intervention, he quickly returned to sport.Discussion/Conclusion: PAES has 6 types. Type 2 (25%) and type 3 (30%) are the most common. Patients with this syndrome suffer from aching pain, numbness, and cramping in the calf area when they exercise. It is necessary to include this disease in differential diagnosis to implement early diagnosis, and ultrasonography is a more cheap and simple method for early detection.Keywords: popliteal artery entrapment syndrome, intermittent claudication

Objective: The study evaluated the association between consumption frequencies of the major food categories and the risk of new depression four years later in older Taiwanese.Design: A prospective cohort study with multistage random sampling. Logistic regression analysis evaluated the significance of the longitudinal associations of intake frequencies of the major food categories with future (4 years later) risk of new depression, controlled for possible confounding factors with or without adjustment for cognitive status.Setting: Population-based free-living elderly.Subjects: Men and women (n 1609) ≥65 years of age.Results: In a regression model that controlled for demographic, socio-economic, lifestyle and disease/health-related variables but not cognitive status, both fruits (OR = 0·66, 95 % CI 0·45, 0·98, P = 0·038) and vegetables (OR = 0·38, 95 % CI 0·17, 0·86, P = 0·021) were protective against depressive symptoms 4 years later. However, when the same regression model was also adjusted for cognitive status, only vegetables (OR = 0·40, 95 % CI 0·17, 0·95, P = 0·039) were protective against depressive symptoms. Higher consumption of eggs was close to being significant in both regression models (P = 0·087 and 0·069, respectively). Other food categories including meat/poultry, fish, seafood, dairy, legumes, grains and tea showed no significant associations.Conclusions: Results suggest that although confounding factors cannot be totally ruled out, more frequent consumption of vegetables seems to be protective against depressive symptoms in the elderly. Further studies are needed to elucidate the causal role and the mechanism of the association. [ABSTRACT FROM AUTHOR]

Study Design: Three-dimensional computed tomography (CT) radiographic analysis. Objective: To describe the parameters for a trajectory through a sacral starting point as a method of pelvic fixation in spinal deformity and to compare this technique with insertion from the posterior superior iliac spine (PSIS). Summary Of Background Data: Long anchors projecting into the ilium provide optimal pelvic fixation. The traditional starting point in the PSIS requires muscle dissection and connectors or rod bends. Methods: Twenty pelvic CTs of mature adolescents were analyzed using InSpace, a three-dimensional CT program, by 2 surgeons. Trajectory with maximal length and width through the sacral ala and iliac wing was obtained through CT imaging plane manipulation. Trajectory and starting-point parameters were measured. Parameters were evaluated and compared for insertion from the PSIS. Results: Based on the ideal trajectory, the mean starting point in S2 was 25 mm caudal to the superior endplate of S1 and 22 mm lateral to the sacral midline (S2 alar-iliac [S2AI] path). Maximal mean S2AI distance was 105 mm (range, 74-129 mm; SD = 11 mm). Maximal mean length for PSIS insertion was 118 mm (range, 99-147 mm; SD = 13 mm). Mean angulation was 40 degrees (SD = 6 degrees ) laterally in the transverse plane and 39 degrees (SD = 6 degrees ) caudally in the sagittal plane. The mean difference between surgeons in selecting the trajectory was 2 degrees and 1 degrees in the transverse and sagittal plane, respectively. The S2AI pathway traversed 35 mm of sacral ala. The narrowest mean width of the ilium along this path was 12 mm (range, 6-18 mm). The starting point for the S2AI was 19 mm deep to the PSIS. The distance from skin for S2AI versus PSIS techniques was 52 and 37 mm, respectively. Conclusion: Iliac fixation through the S2 ala provides a reproducibly chosen starting point in line with S1 pedicle anchors. Implant prominence is minimized because the starting point is 15 mm deeper than the PSIS entry. It is less likely to be affected in cases using iliac crest bone graft harvest because of the more anterior position of the anchor in the ilium. [ABSTRACT FROM AUTHOR]

The present study evaluated functional properties of lactic-fermented ginger products. Three Zingiberaceae species were used as the substrate for fermentation using three lactic acid bacteria. The fermentation process ended 35-40 h after inoculation and reached a pH value of 3.5-4.0. Total antioxidant performances were 68-75%, and were best observed using Bifidobacterium longum as the starter in three ginger samples. DPPH scavenging was on average 70%, with free radical anion scavenging and peroxide removal effects of 30.6% and 43.7%, respectively. The product acceptance survey showed that the 100% fermented juice without a mixture with non-fermented ginger juice obtained the highest score in overall performance. The lactic-fermented Vanoverberghia and Hedychium ginger species retained an antioxidant activity and DPPH scavenging activity of on average 70%. This study may suggest a new way of ginger food processing with high functionality. Also, it may help to popularize the growing and processing of endemic ginger plants in Taiwan. [ABSTRACT FROM AUTHOR]

Purpose: To examine the behavior and function of human gingival fibroblasts growing on healing abutments with or without laser-textured topography., Materials and Methods: Human primary gingival connective tissue fibroblasts were cultured on healing abutments with machined or laser-textured (Laser-Lok, BioHorizons) surfaces. Cellular and molecular responses were evaluated by a variety of tests, including cell density assay (WST-1), fluorescence microscopy, real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and detachment tests., Results: The machined surface showed monodirectional traces and scratches from milling, whereas the laser-textured surface showed a distinct morphology consisting of monodirectional mesoscale channels (15-μm pitch) and woven oblique microridges formed within the channels. There were no differences in initial fibroblast attachment, subsequent fibroblast proliferation, or collagen production between the machined and laser-textured surfaces. Fibroblasts growing on a laser-textured surface were found to spread in one direction along the mesochannels, while cells growing on machined surfaces tended to spread randomly. Fibroblasts on laser-textured surfaces were 1.8 times more resistant to detachment than those on machined surfaces. An adhesive glycoprotein (fibronectin) and transmembrane adhesion linker gene (integrin β-1) were upregulated on laser-textured surfaces., Conclusions: The increased fibroblast retention, uniform growth, and increased transcription of cell adhesion proteins compellingly explain the enhanced tissue-level response to laser-created and hybrid-textured titanium surfaces. These results provide a cellular and molecular rationale for the tissue reaction to this unique surface; in addition, they support its extended use, from implants and healing abutments to diverse prosthetic components where enhanced soft tissue responses would be desirable.

Dysfunctional voiding (DV) is an abnormal urethral sphincter activity during voiding in neurologically normal individuals. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to treat DV, but the results have not been completely satisfactory. This study investigated the neurological characteristics of women with DV using the lower urinary tract electrophysiology (EP) study and the therapeutic efficacy of BoNT-A injection. In total, 48 women with DV and 16 women with normal voiding were included. Videourodynamic studies were conducted to diagnose DV before BoNT-A injection. EP studies, including urethral sphincter electromyography, bulbocavernosus reflex, and pudendal nerve conduction velocity, were conducted. Polyphasic motor unit action potentials suggestive of reinnervation were detected in 58.3% of patients with DV and 18.8% of controls ( p = 0.001). Significant improvement in the corrected maximum flow rate (cQmax) was observed in patients with reinnervation at 1 and 3 months after BoNT-A injections into the urethral sphincter. Urethral sphincter denervation or reinnervation activity was commonly noted in 62.5% of women with DV. Repeated BoNT-A injections into the urethral sphincter provided effective treatment in 47.9% of patients, with mild improvement in cQmax observed in patients with urethral sphincter reinnervation. However, the improvement was not superior to those without reinnervation.

We developed an inherently interpretable multilevel Bayesian framework for representing variation in regression coefficients that mimics the piecewise linearity of ReLU-activated deep neural networks. We used the framework to formulate a survival model for using medical claims to predict hospital readmission and death that focuses on discharge placement, adjusting for confounding in estimating causal local average treatment effects. We trained the model on a 5% sample of Medicare beneficiaries from 2008 and 2011, based on their 2009-2011 inpatient episodes (approximately 1.2 million), and then tested the model on 2012 episodes (approximately 400 thousand). The model scored an out-of-sample AUROC of approximately 0.75 on predicting all-cause readmissions-defined using official Centers for Medicare and Medicaid Services (CMS) methodology-or death within 30-days of discharge, being competitive against XGBoost and a Bayesian deep neural network, demonstrating that one need-not sacrifice interpretability for accuracy. Crucially, as a regression model, it provides what blackboxes cannot-its exact gold-standard global interpretation, explicitly defining how the model performs its internal "reasoning" for mapping the input data features to predictions. In doing so, we identify relative risk factors and quantify the effect of discharge placement. We also show that the posthoc explainer SHAP provides explanations that are inconsistent with the ground truth model reasoning that our model readily admits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

CCR5-tropic simian/human immunodeficiency viruses (SHIV) with clade C transmitted/founder envelopes represent a critical tool for the investigation of HIV experimental vaccines and microbicides in nonhuman primates, although many such isolates lead to spontaneous viral control post infection. Here, we generated a high-titer stock of pathogenic SHIV-C109p5 by serial passage in two rhesus macaques (RM) and tested its virulence in aged monkeys. The co-receptor usage was confirmed before infecting five geriatric rhesus macaques (four female and one male). Plasma viral loads were monitored by reverse transcriptase-quantitative PCR (RT-qPCR), cytokines by multiplex analysis, and biomarkers of gastrointestinal damage by enzyme-linked immunosorbent assay. Antibodies and cell-mediated responses were also measured. Viral dissemination into tissues was determined by RNAscope. Intravenous SHIV-C109p5 infection of aged RMs leads to high plasma viremia and rapid disease progression; rapid decrease in CD4 + T cells, CD4 + CD8 + T cells, and plasmacytoid dendritic cells; and wasting necessitating euthanasia between 3 and 12 weeks post infection. Virus-specific cellular immune responses were detected only in the two monkeys that survived 4 weeks post infection. These were Gag-specific TNFα+CD8+, MIP1β+CD4+, Env-specific IFN-γ+CD4+, and CD107a+ T cell responses. Four out of five monkeys had elevated intestinal fatty acid binding protein levels at the viral peak, while regenerating islet-derived protein 3α showed marked increases at later time points in the three animals surviving the longest, suggesting gut antimicrobial peptide production in response to microbial translocation post infection. Plasma levels of monocyte chemoattractant protein-1, interleukin-15, and interleukin-12/23 were also elevated. Viral replication in gut and secondary lymphoid tissues was extensive.IMPORTANCESimian/human immunodeficiency viruses (SHIV) are important reagents to study prevention of virus acquisition in nonhuman primate models of HIV infection, especially those representing transmitted/founder (T/F) viruses. However, many R5-tropic SHIV have limited fitness in vivo leading to many monkeys spontaneously controlling the virus post acute infection. Here, we report the generation of a pathogenic SHIV clade C T/F stock by in vivo passage leading to sustained viral load set points, a necessity to study pathogenicity. Unexpectedly, administration of this SHIV to elderly rhesus macaques led to extensive viral replication and fast disease progression, despite maintenance of a strict R5 tropism. Such age-dependent rapid disease progression had previously been reported for simian immunodeficiency virus but not for R5-tropic SHIV infections., Competing Interests: The authors declare no conflict of interest.

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens-bis-acrylic 1 and 2, flowable and bulk-fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control-were fabricated in rectangular plates ( n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20-30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk-fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.

Interferon ɛ (IFNɛ) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections. Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNɛ contributes to protection against ZIKV infection in vivo is unknown. In this study, we show that IFNɛ plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNɛ was expressed not only by epithelial cells in the FRT but also by immune and stromal cells at baseline or after exposure to viruses or specific Toll-like receptor (TLR) agonists. IFNɛ-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal but not subcutaneous ZIKV infection. IFNɛ deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNɛ protected Ifnɛ -/- mice and highly susceptible Ifnar1 -/- mice against vaginal ZIKV infection, indicating that IFNɛ was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFNɛ in mediating protection against the transmission of ZIKV in the context of sexual contact., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication-competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Distinct viral dynamics were seen in hTERT TIGKs compared to A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells on day 3 after infection. Analysis of oral epithelial cells infected by replication-competent SARS-CoV-2 viruses expressing GFP showed that the GFP signal and SARS-CoV-2 mRNAs were not evenly distributed. Furthermore, we found cumulative SARS-CoV-2 RNAs from released viruses in the media from oral epithelial cells on day 1 and day 2 after infection, indicating productive viral infection. Taken together, our results demonstrated that oral epithelial cells were susceptible to SARS-CoV-2 viruses despite low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for the development of future vaccines and therapeutics.

Hydrogels are extensively used as tunable, biomimetic three-dimensional cell culture matrices, but optically deep, high-resolution images are often difficult to obtain, limiting nanoscale quantification of cell-matrix interactions and outside-in signalling. Here we present photopolymerized hydrogels for expansion microscopy that enable optical clearance and tunable ×4.6-6.7 homogeneous expansion of not only monolayer cell cultures and tissue sections, but cells embedded within hydrogels. The photopolymerized hydrogels for expansion microscopy formulation relies on a rapid photoinitiated thiol/acrylate mixed-mode polymerization that is not inhibited by oxygen and decouples monomer diffusion from polymerization, which is particularly beneficial when expanding cells embedded within hydrogels. Using this technology, we visualize human mesenchymal stem cells and their interactions with nascently deposited proteins at <120 nm resolution when cultured in proteolytically degradable synthetic polyethylene glycol hydrogels. Results support the notion that focal adhesion maturation requires cellular fibronectin deposition; nuclear deformation precedes cellular spreading; and human mesenchymal stem cells display cell-surface metalloproteinases for matrix remodelling., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Goals: The aim was to investigate the adenoma detection rate (ADR) of endoscopists who have used full-spectrum endoscopy (Fuse) for 3 years and revert back to traditional forward-viewing endoscopes (R-TFV) at an ambulatory surgical center., Background: Traditional forward viewing (TFV) endoscopes have 1 camera and provide an angle of view of 140 to 170 degrees, whereas Fuse provides a 330 degrees view through the addition of 2 side cameras. It has previously been reported that Fuse increased the ADR by 5.4% when compared with previous rates using TFV. Fuse is no longer commercially available. The ADR of endoscopists who revert back to TFV is unknown., Study: We conducted a retrospective analysis of data examining the ADR from average risk screening colonoscopies at a 5-room ambulatory surgical center where endoscopists transitioned from TFV to Fuse in April 2014 and then reverted back to TFV in 2016. The primary outcome was ADR. Secondary outcomes were ADR for advanced and right-sided adenomas., Results: A total of 6110 procedures were reviewed. The ADR was 23.70% for TFV, 29.02% for Fuse and 28.88% for R-TFV. The ADR for advanced adenomas was 3.8% for TFV, 6.0% for Fuse and 7.3% for R-TFV. The ADR for right-sided adenomas was 13.0% for TFV, 16.7% for Fuse and 16.0% for R-TFV. The results for all 3 categories showed a statistical difference between TFV and Fuse as well as between TFV and R-TFV. There were no statistical differences between the ADR of Fuse compared with R-TFV., Conclusions: During R-TFV, endoscopists are able to maintain their increased ability to detect adenomas. This would suggest that there was a change in behavior in endoscopists using Fuse that was durable., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Light-cured composite resins are widely used in dental restorations to fill cavities and fabricate temporary crowns. After curing, the residual monomer is a known to be cytotoxic, but increasing the curing time should improve biocompatibility. However, a biologically optimized cure time has not been determined through systematic experimentation. The objective of this study was to examine the behavior and function of human gingival fibroblasts cultured with flowable and bulk-fill composites cured for different periods of time, while considering the physical location of the cells with regard to the materials. Biological effects were separately evaluated for cells in direct contact with, and in close proximity to, the two composite materials. Curing time varied from the recommended 20 s to 40, 60, and 80 s. Pre-cured, milled-acrylic resin was used as a control. No cell survived and attached to or around the flowable composite, regardless of curing time. Some cells survived and attached close to (but not on) the bulk-fill composite, with survival increasing with a longer curing time, albeit to <20% of the numbers growing on milled acrylic even after 80 s of curing. A few cells (<5% of milled acrylic) survived and attached around the flowable composite after removal of the surface layer, but attachment was not cure-time dependent. Removing the surface layer increased cell survival and attachment around the bulk-fill composite after a 20-s cure, but survival was reduced after an 80-s cure. Dental-composite materials are lethal to contacting fibroblasts, regardless of curing time. However, longer curing times mitigated material cytotoxicity exclusively for bulk-fill composites when the cells were not in direct contact. Removing the surface layer slightly improved biocompatibility for cells in proximity to the materials, but not in proportion to cure time. In conclusion, mitigating the cytotoxicity of composite materials by increasing cure time is conditional on the physical location of cells, the type of material, and the finish of the surface layer. This study provides valuable information for clinical decision making and novel insights into the polymerization behavior of composite materials.

A common complication with the use of acrylic resin denture teeth is wear of the occlusal surfaces. Modifying the occlusal surfaces with gold onlays has been suggested to combat this phenomenon. This clinical report describes the use of zirconia as an alternative material on a patient with increased tendencies for occlusal wear. The advantages of using zirconia include wear resistance, decreased cost, and straightforward fabrication., (Published by Elsevier Inc.)

Cirrhosis is a major cause of global morbidity and mortality, and significantly leads to a heightened risk of liver cancer. Despite decades of efforts in seeking for cures for cirrhosis, this disease remains irreversible. To assist in the advancement of understanding toward cirrhosis as well as therapeutic options, various disease models, each with different strengths, are developed. With the development of three-dimensional (3D) cell culture in recent years, more realistic biochemical properties are observed in 3D cell models, which have gradually taken over the responsibilities of traditional 2D cell culture, and are expected to replace some of the animal models in the near future. Here, we propose a 3D fibrotic liver model inspired by liver lobules. In the model, 3D-printed poly(glycerol sebacate) acrylate (PGSA) scaffolds facilitated the formation of 3D tissues and guided the deposition of fibrotic structures. Through the sequential seeding of hepatic stellate cells (HSCs), HepG2 and HSCs, fibrotic septum-like tissues were created on PGSA scaffolds. As albumin secretion is considered a rather important function of the liver and is found only among hepatic cells, the detection of albumin secretion up to 30 days indicates the mimicking of basic liver functions. Moreover, the in vivo fibrotic tissue shows a high similarity to fibrotic septa. Finally, via complete encapsulation of HSCs, a down-regulated albumin secretion profile was observed in the capped model, which is a metabolic indicator that is important for the prognosis for liver cirrhosis. Looking forward, the incorporation of the vasculature will further upgrade the model into a sound tool for liver research and associated treatments.

The surface-supported silver nanoparticles have been studied and applied in various applications. Many unique nanostructures have been introduced into this field to improve the functionalities of the surfaces depending on application purposes. We created featured silver nano-array surfaces by utilizing the solvent-mediated phase transition on the surface grafted with poly (acrylic) acids polymer chains and taking advantage of the low temperature of argon gas discharged plasma as a reducing agent. The applied solvents and grafted polymer chain densities affected the phase transition and thus determined the outcome of surface nano-array patterns. However, the total loaded silver ions on the surface affected silver nano-array structures at the sub-micron levels. The featured silver patterned surfaces made in the optimal conditions present a favorable surface-enhanced Raman spectroscopy enhancement as well as recyclability for detection re-usage. This novel method prepares tunable silver nanopatterned surfaces and provides a new approach to various potential applications., (© 2022 IOP Publishing Ltd.)

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is highly contagious and remains a major public health challenge despite the availability of effective vaccines. SARS-CoV-2 enters cells through the binding of its spike receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor in concert with accessory receptors/molecules that facilitate viral attachment, internalization, and fusion. Although ACE2 plays a critical role in SARS-CoV-2 replication, its expression profiles are not completely associated with infection patterns, immune responses, and clinical manifestations. Additionally, SARS-CoV-2 infects cells that lack ACE2, and the infection is resistant to monoclonal antibodies against spike RBD in vitro, indicating that some human cells possess ACE2-independent alternative receptors, which can mediate SARS-CoV-2 entry. Here, we discuss these alternative receptors and their interactions with SARS-CoV-2 components for ACE2-independent viral entry. These receptors include CD147, AXL, CD209L/L-SIGN/CLEC4M, CD209/DC-SIGN/CLEC4L, CLEC4G/LSECtin, ASGR1/CLEC4H1, LDLRAD3, TMEM30A, and KREMEN1. Most of these receptors are known to be involved in the entry of other viruses and to modulate cellular functions and immune responses. The SARS-CoV-2 omicron variant exhibits altered cell tropism and an associated change in the cell entry pathway, indicating that emerging variants may use alternative receptors to escape the immune pressure against ACE2-dependent viral entry provided by vaccination against RBD. Understanding the role of ACE2-independent alternative receptors in SARS-CoV-2 viral entry and pathogenesis may provide avenues for the prevention of infection by SARS-CoV-2 variants and for the treatment of COVID-19.

Purpose: Voiding dysfunction is common in patients with chronic central nervous system (CNS) diseases and has great impact on quality of life. Patients with chronic CNS disorders might have concomitant detrusor overactivity, detrusor underactivity, and voiding dysfunction. Although bladder outlet surgeries could relieve bladder outlet obstruction (BOO), patients might have persistent or exacerbated storage symptoms. This study investigated surgical outcome of patients with chronic CNS disorders after bladder outlet surgery., Methods: A total of 63 male patients with cerebrovascular accident (CVA, n = 44), Parkinson's disease (PD, n = 11), and early-stage dementia (n = 8), had received bladder outlet surgery after videourodynamic proven BOO refractory to medical treatment. The preoperative and postoperative lower urinary tract symptoms (LUTS) and uroflowmetry parameters were assessed. If the storage symptom subscore decreased or increased by 1, the outcome was considered improved or exacerbated after treatment. When patients had improvement in maximum flow rate (Qmax) and voiding efficiency (VE) and decreased voiding symptom subscore, they were considered having improvement of voiding dysfunction., Results: The mean age was 71.1 ± 9.8 years and mean duration from diagnosis of BOO to surgical intervention was 15.1 ± 25.0 months. Overall, there was significant improvement in voiding LUTS and urinary retention after surgery. The post-void residual volume (PVR), corrected Qmax (cQmax), and VE significantly improved after surgery. In subgroup analysis, although voiding symptoms improved in CVA patients, urgency and exacerbated urgency incontinence persisted after surgery. In PD patients, there was improvement in voiding condition such as PVR, cQmax and VE, but the storage symptoms did not change after surgery. Patients with dementia had no improvement both in storage and voiding symptoms., Conclusions: Bladder outlet surgeries are effective to relieve voiding dysfunction in patients with CVA and PD, but have little effect on storage LUTS in patients with chronic brain lesions., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The Coronavirus disease 2019 (COVID-19) pandemic disproportionately affects immunocompetent and immunocompromised individuals, with the latter group being more vulnerable to severe disease and death. However, the differential pathogenesis of SARS-CoV-2 in the context of a specific immunological niche remains unknown. Similarly, systematic analysis of disease pathology in various extrapulmonary organs in immunocompetent and immunocompromised hosts during SARS-CoV-2 infection is not fully understood. We used a hamster model of SARS-CoV-2 infection, which recapitulates the pathophysiology of patients with mild-to-moderate COVID-19, to determine the dynamics of SARS-CoV-2 replication and histopathology at organ-level niches and map how COVID-19 symptoms vary in different immune contexts. Hamsters were intranasally infected with low (LD) or high (HD) inoculums of SARS-CoV-2, and the kinetics of disease pathology and viral load in multiple organs, antibody response, inflammatory cytokine expression, and genome-wide lung transcriptome by RNAseq analysis were determined and compared against corresponding responses from chemically induced immunocompromised hamsters. We observed transient body weight loss proportional to the SARS-CoV-2 infectious dose in immunocompetent hamsters. The kinetics of viral replication and peak viral loads were similar between LD and HD groups, although the latter developed more severe disease pathology in organs. Both groups generated a robust serum antibody response. In contrast, infected immunocompromised animals showed more prolonged body weight loss and mounted an inadequate SARS-CoV-2-neutralizing antibody response. The live virus was detected in the pulmonary and extrapulmonary organs for extended periods. These hamsters also had persistent inflammation with severe bronchiolar-alveolar hyperplasia/metaplasia. Consistent with the differential disease presentation, distinct changes in inflammation and immune cell response pathways and network gene expression were seen in the lungs of SARS-CoV-2-infected immunocompetent and immunocompromised animals.

A facile method for preparing hierarchical carbon composites that contain activated carbon (AC), carbon nanospheres (CNSs), and carbon nanotubes (CNTs) for use as the electrode material in supercapacitors (SCs) was developed. The CNS/CNT network enabled the formation of three-dimensional conducting pathways within the highly porous AC matrix, effectively reducing the internal resistance of an SC electrode. The specific capacitance, cyclability, voltage window, temperature profile during charging/discharging, leakage current, gas evolution, and self-discharge of the fabricated SCs were systematically investigated and the optimal CNS/CNT ratio was determined. A 2.5 V floating aging test at 70 °C was performed on SCs made with various hierarchical carbon electrodes. Electrochemical impedance spectroscopy, postmortem electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy analyses were conducted to examine the electrode aging behavior. A hierarchical carbon architecture with an appropriate AC/CNS/CNT constituent ratio could significantly improve charge-discharge performance, increase cell reliability, and decrease the aging-related degradation rate., (© 2022 Wiley-VCH GmbH.)

Brilacidin (PMX-30063), a non-peptide defensin-mimetic small molecule, inhibits SARS-CoV-2 viral infection but the anti-viral mechanism is not defined. Here we determined its effect on the specific step of the viral life cycle. Brilacidin blocked SARS-CoV-2 infection but had no effect after viral entry. Brilacidin inhibited pseudotyped SARS-CoV-2 viruses expressing spike proteins from the P.1 Brazil strain and the B.1.1.7 UK strain. Brilacidin affected viral attachment in hACE2-dependent and independent manners depending on the concentrations. The inhibitory effect on viral entry was not mediated through blocking the binding of either the spike receptor-binding domain or the spike S1 protein to hACE2 proteins. Taken together, brilacidin inhibits SARS-CoV-2 infection by blocking viral entry and is active against SARS-CoV-2 variants., Competing Interests: Disclosure Statement Authors declare that there is no conflict of interest except that J. A. H. and W. K. W. are employees of Innovation Pharmaceuticals, Inc.

Sexual contact is the most common route of HIV transmission, and the concurrent presence of sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (gonococcus, GC) is known to increase the HIV risk. Antibiotic treatment decreases the incidence of STIs but not HIV. CT and GC activate Toll-like receptors (TLRs) 2 and 4, which act as sensors of microbial infection are critical for initiating immune responses to control infection. We have previously shown that GC enhances HIV infection of primary resting CD4+ T cells through activation of TLR2 but not TLR4. In this study, we determined the effect of live and fixed CT and different species of lactobacilli including L. jensenii and L. reuteri on HIV infection of freshly isolated PBMCs. We found that pretreatment of freshly isolated PBMCs with fresh or fixed CT, but not lactobacilli , promoted HIV infection of freshly isolated CD4+ T cells. Together with our previous reports, we concluded that STIs such as CT and GC but not commensal bacteria like lactobacilli enhanced HIV infection, possibly through immune activation. Importantly, the enhancement effect of fixed CT on HIV infection may explain the failure of antibiotic treatments to reduce the HIV incidence. Combined strategies to inhibit STI growth and STI-mediated mucosal immune activation should be considered for HIV prevention in the settings of STIs.

Background: Unilateral vocal fold paralysis (UVFP) caused by lung surgery is associated with prolonged hospital stay and increased postoperative comorbidities. We evaluated lung surgery-related UVFP and compared its characteristics with UVFP caused by esophageal and thyroid surgeries, as the most common surgical causes of UVFP. We also evaluated the outcomes of intracordal hyaluronate injection laryngoplasty in these patients., Methods: Patients with surgery-related UVFP were evaluated by quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, Voice Outcome Survey (VOS) questionnaire, and Short Form-36 Health Survey (SF-36) quality-of-life questionnaire. Data for the lung, esophageal, and thyroid surgery groups were compared and changes in outcome measurements induced by hyaluronate injection were compared among the three groups., Results: A total of 141 patients were recruited, including 21, 46, and 74 in the lung, esophageal, and thyroid surgery groups, respectively. Compared with the other two groups, lung surgery patients had predominantly left-sided UVFP, less involvement of the external branch of the superior laryngeal nerve, and higher jitter. Most outcome measurements improved in all three groups after office-based hyaluronate injection, with the greatest improvement in jitter in the lung surgery group., Conclusions: Lung surgery-related UVFP showed a distinct disease presentation, and patients' voice parameters and quality of life recovered dramatically after office-based hyaluronate injection. We recommend evaluation of lung surgery-related UVFP and early intervention, such as office-based hyaluronate injection, to improve patients' voice function and quality of life., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Skeletal muscle tissue is mechanically dynamic with changes in stiffness influencing function, maintenance, and regeneration. We modeled skeletal muscle mechanical changes in culture with dynamically stiffening hydrogels demonstrating that the chaperone protein BAG3 transduces matrix stiffness by redistributing YAP and TAZ subcellular localization in muscle progenitor cells. BAG3 depletion increases cytoplasmic retention of YAP and TAZ, desensitizing myoblasts to changes in hydrogel elastic moduli. Upon differentiation, muscle progenitors depleted of BAG3 formed enlarged, round myotubes lacking the typical cylindrical morphology. The aberrant morphology is dependent on YAP/TAZ signaling, which was sequestered in the cytoplasm in BAG3-depleted myotubes but predominately nuclear in cylindrical myotubes of control cells. Control progenitor cells induced to differentiate on soft (E' = 4 and 12 kPa) hydrogels formed circular myotubes similar to those observed in BAG3-depleted cells. Inhibition of the Hippo pathway partially restored myotube morphologies, permitting nuclear translocation of YAP and TAZ in BAG3-depleted myogenic progenitors. Thus, BAG3 is a critical mediator of dynamic stiffness changes in muscle tissue, coupling mechanical alterations to intracellular signals and inducing changes in gene expression that influence muscle progenitor cell morphology and differentiation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Tuberculosis (TB) is a global health threat that affects 10 million people worldwide. Human Immunodeficiency Virus (HIV) remains one of the major contributors to the reactivation of asymptomatic latent tuberculosis (LTBI). Over the recent years, there has been a significant focus in developing in-vitro 3D models mimicking early events of Mycobacterium tuberculosis (Mtb) pathogenesis, especially formation of the granuloma. However, these models are low throughput and require extracellular matrix. In this article, we report the generation of a matrix-free 3D model, using THP-1 human monocyte/macrophage cells and mCherry-expressing Mycobacterium bovis BCG (Bacilli Camille Guérin), henceforth referred as 3D spheroids, to study the host cell-bacterial interactions. Using mCherry-intensity-based tracking, we monitored the kinetics of BCG growth in the 3D spheroids. We also demonstrate the application of the 3D spheroids for testing anti-TB compounds such as isoniazid (INH), rifampicin (RIF), as well as a host-directed drug, everolimus (EVR) as single and combinational treatments. We further established a dual infection 3D spheroid model by coinfecting THP-1 macrophages with BCG mCherry and pseudotype HIV. In this HIV-TB co-infection model, we found an increase in BCG mCherry growth within the 3D spheroids infected with HIV pseudotype. The degree of disruption of the granuloma was proportional to the virus titers used for co-infection. In summary, this 3D spheroid assay is an useful tool to screen anti-TB response of potential candidate drugs and can be adopted to model HIV-TB interactions., (© 2021 Shilpaa Mukundan et al., published by Sciendo.)

Here we present derived thermal-hydrological variations data during the Marine isotope stages (MISs) 10-12 using surface and subsurface dwelling planktonic foraminiferal geochemical proxies of a sedimentary core of MD05-2925 (9.3 o S, 151.5 o E, water depth 1661 m, core depth 1842-2430 cm), Solomon Sea. Globigerinoides ruber ( s.s. , white, 250-300 µm) and Pulleniatina obliquiloculata (355-425 µm) tests were hand-picked and cleaned for stable carbon and oxygen isotopes and Mg/Ca analyses. Composite benthic foraminifera tests (>250 µm, Uvigerina spp. , and Bulimina spp. ) are also hand-picked and cleaned for stable oxygen isotope stratigraphy. In total, 235 and 148 measurements for C-O stable isotopes and Mg/Ca ratios for planktonic foraminifera in 2-5 cm resolution for the period from 352.1 to 462.3 ka are presented in this data report, respectively. Age model is established by tuning composite benthic foraminiferal oxygen isotope to global composite benthic foraminifera oxygen isotope stack LR04. Surface and subsurface temperatures and seawater oxygen isotopes (δ 18 O W , without ice volume correction) were calculated., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 Published by Elsevier Inc.)

Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and is likely to contribute to COVID-19 disease outcomes. Defensins are highly abundant innate immune factors in neutrophils and epithelial cells, including intestinal Paneth cells, and exhibit antimicrobial and immune-modulatory activities. In this study, we investigated the effects of human α- and β-defensins and RC101, a θ-defensin analog, on SARS-CoV-2 infection. We found that human neutrophil peptides (HNPs) 1-3, human defensin (HD) 5 and RC101 exhibited potent antiviral activity against pseudotyped viruses expressing SARS-CoV-2 spike proteins. HNP4 and HD6 had weak anti-SARS-CoV-2 activity, whereas human β-defensins (HBD2, HBD5 and HBD6) had no effect. HNP1, HD5 and RC101 also inhibited infection by replication-competent SARS-CoV-2 viruses and SARS-CoV-2 variants. Pretreatment of cells with HNP1, HD5 or RC101 provided some protection against viral infection. These defensins did not have an effect when provided post-infection, indicating their effect was directed towards viral entry. Indeed, HNP1 inhibited viral fusion but not the binding of the spike receptor-binding domain to hACE2. The anti-SARS-CoV-2 effect of defensins was influenced by the structure of the peptides, as linear unstructured forms of HNP1 and HD5 lost their antiviral function. Pro-HD5, the precursor of HD5, did not block infection by SARS-CoV-2. High virus titers overcame the effect of low levels of HNP1, indicating that defensins act on the virion. HNP1, HD5 and RC101 also blocked viral infection of intestinal and lung epithelial cells. The protective effects of defensins reported here suggest that they may be useful additives to the antivirus arsenal and should be thoroughly studied.

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), enters cells through attachment to the human angiotensin converting enzyme 2 (hACE2) via the receptor-binding domain (RBD) in the surface/spike (S) protein. Several pseudotyped viruses expressing SARS-CoV-2 S proteins are available, but many of these can only infect hACE2-overexpressing cell lines. Here, we report the use of a simple, two-plasmid, pseudotyped virus system comprising a SARS-CoV-2 spike-expressing plasmid and an HIV vector with or without vpr to investigate the SARS-CoV-2 entry event in various cell lines. When an HIV vector without vpr was used, pseudotyped SARS-CoV-2 viruses produced in the presence of fetal bovine serum (FBS) were able to infect only engineered hACE2-overexpressing cell lines, whereas viruses produced under serum-free conditions were able to infect a broader range of cells, including cells without hACE2 overexpression. When an HIV vector containing vpr was used, pseudotyped viruses were able to infect a broad spectrum of cell types regardless of whether viruses were produced in the presence or absence of FBS. Infection sensitivities of various cell types did not correlate with mRNA abundance of hACE2, TMPRSS2, or TMPRSS4. Pseudotyped SARS-CoV-2 viruses and replication-competent SARS-CoV-2 virus were equally sensitive to neutralization by an anti-spike RBD antibody in cells with high abundance of hACE2. However, the anti-spike RBD antibody did not block pseudotyped viral entry into cell lines with low abundance of hACE2. We further found that CD147 was involved in viral entry in A549 cells with low abundance of hACE2. Thus, our assay is useful for drug and antibody screening as well as for investigating cellular receptors, including hACE2, CD147, and tyrosine-protein kinase receptor UFO (AXL), for the SARS-CoV-2 entry event in various cell lines.

The need for new antibiotics is increasing due to their overuse, and antibiotic resistance has become one of the major threats worldwide to public health, food safety, and clinical treatment. In this study, we describe an actinobacterial isolate, YX44, which belongs to the genus Streptomyces . This Streptomyces was isolated from a drinking pipe located in Osaka, Japan, and has the ability to inhibit Gram-positive bacteria, Gram-negative bacteria, and various fungi. YX44 fermentation broth shows strong activity against Escherichia coli and Staphylococcus aureus , as well as also inhibiting clinical isolates of multidrug-resistant Staphylococcus aureus . The YX44 antibacterial substances in the broth are relatively heat-stable, show high stability from the pH range 1 to 11, and have good solubility in both organic and non-organic solvents. Size-exclusion chromatography revealed that the YX44 antibacterial compounds are less than 1000 Da in size. LC-MS was able to identify three possible candidate molecules with molecular weights of 308, 365, 460, and 653 g/mol; none of these sizes correspond to any well-known antibiotics. Our results show that Streptomyces sp. YX44 seems to produce a number of novel antibiotics with high pH stability and good solubility that have significant activity against S. aureus, including multidrug-resistant strains.

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) is detectable in saliva from asymptomatic individuals, suggesting a potential benefit from the use of mouth rinses to suppress viral load and reduce virus spread. Published studies on the reduction of SARS-CoV-2-induced cytotoxic effects by mouth rinses do not exclude antiseptic mouth rinse-associated cytotoxicity. Here, we determined the effect of commercially available mouth rinses and antiseptic povidone-iodine on the infectivity of replication-competent SARS-CoV-2 viruses and of pseudotyped SARS-CoV-2 viruses. We first determined the effect of mouth rinses on cell viability to ensure that antiviral activity was not a consequence of mouth rinse-induced cytotoxicity. Colgate Peroxyl (hydrogen peroxide) exhibited the most cytotoxicity, followed by povidone-iodine, chlorhexidine gluconate (CHG), and Listerine (essential oils and alcohol). The potent antiviral activities of Colgate Peroxyl mouth rinse and povidone-iodine were the consequence of rinse-mediated cellular damage when the products were present during infection. The potency of CHG was greater when the product was not washed off after virus attachment, suggesting that the prolonged effect of mouth rinses on cells impacts the antiviral outcome. To minimalize mouth rinse-associated cytotoxicity, mouth rinse was largely removed from treated viruses by centrifugation prior to infection of cells. A 5% ( v / v ) dilution of Colgate Peroxyl or povidone-iodine completely blocked viral infectivity. A similar 5% ( v / v ) dilution of Listerine or CHG had a moderate suppressive effect on the virus, but a 50% ( v / v ) dilution of Listerine or CHG blocked viral infectivity completely. Mouth rinses inactivated the virus without prolonged incubation. The new infectivity assay, with limited impacts of mouth rinse-associated cytotoxicity, showed the differential effects of mouth rinses on SARS-CoV-2 infection. Our results indicate that mouth rinses can significantly reduce virus infectivity, suggesting a potential benefit for reducing SARS-CoV-2 spread.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin-a de novo designed synthetic small molecule that captures the biological properties of HDPs-on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture., Competing Interests: Warren K. Weston serves as a consultant for Innovation Pharmaceuticals Inc. Jane A. Harness is an employee of Innovation Pharmaceuticals Inc.

Lots of lithium ion battery (LIB) products contain lithium metal oxide LiNi 5 Co 2 Mn 3 O 2 (LNCM) as the positive electrode's active material. The stable surface of this oxide results in high resistivity in the battery. For this reason, conductive carbon-based materials, including acetylene black and carbon black, become necessary components in electrodes. Recently, carbon nano-tube (CNT) has appeared as a popular choice for the conductive carbon in LIB. However, a large quantity of the conductive carbon, which cannot provide capacity as the active material, will decrease the energy density of batteries. The ultra-high cost of CNT, compared to conventional carbon black, is also a problem. In this work, we are going to introduce long-length carbon nano-tube s(L-CNT) into electrodes in order to design a reduced-amount conductive carbon electrode. The whole experiment will be done in a 1Ah commercial type pouch LIB. By decreasing conductive carbon as well as increasing the active material in the positive electrode, the energy density of the LNCM-based 1Ah pouch type LIB, with only 0.16% of L-CNT inside the LNCM positive electrode, could reach 224 Wh/kg and 549 Wh/L, in weight and volume energy density, respectively. Further, this high energy density LIB with L-CNT offers stable cyclability, which may constitute valuable progress in portable devices and electric vehicle (EV) applications.

The regeneration of damaged or lost tissue is considered to be a critical step toward realizing full organ regeneration in modern medicine. Although surgical techniques continue to advance, treatment for missing tissues in irregular wounds remains particularly difficult. With increasing interest in the application of additive manufacturing in tissue engineering, the fabrication of customized scaffolds for the regeneration of missing tissue via three-dimensional (3D) printing has become especially promising. Amongst the work on the regeneration of many important organs, liver regeneration is particularly interesting because liver diseases are increasingly prevalent in many countries around the world, resulting in a greater need for liver transplantation. The generation of hexagonal scaffolds for the regeneration of liver lobules is highly demanding, but their 3D structure has been proved difficult to reproduce by traditional fabrication methods. In this work, various hexagonal scaffolds are developed for liver lobule regeneration via 3D printing using novel biodegradable polymeric materials, including poly(glycerol sebacate) acrylate and poly(ethylene glycol) diacrylate. Through fine-tuning of printing parameters, a series of hexagonal scaffolds were designed and printed to mimic liver lobule units. The scaffolds were printed with various structures together with varying surface areas and 3D structures to enhance cell seeding density and diffusivity of the culture medium. Analysis of cell metabolic activities showed that the high-diffusion staircase (HDS) scaffold could support potential differences in cell proliferation rate. Furthermore, the HDS scaffolds composed of different copolymers were cultured with cells for up to 16 days to investigate the relationship between physical properties and hepatocyte proliferation. The results indicate that the combination of the high flexibility 3D printing with biodegradable, photocurable copolymers shows great promise for the regeneration of 3D liver lobules.

The AgBrO₃/few-layer g-C₃N₄ composite photocatalyst has been developed via an in-situ synthetic method. The structure, morphology, light response range, separation and migration efficiency of the photogenerated electron-hole pairs and element valence state of the as-obtained samples have been characterized. The tetracycline was used to discuss the photocatalytic activities of the samples. The photocatalytic degradation mechanism of the as-obtained composites was also researched. The analysis results show that the photocatalytic degradation property of the asobtained composite photocatalyst appears to the tendency of first increasing and then decreasing with increasing the amount of AgBrO₃ under visible light illumination. When the mass ratio of AgBrO₃ to g-C₃N₄ is 4:3, in 60 min, the photocatalytic degradation efficiency of the as-obtained composites reaches the maximum of 79%. It is 37% and 45% higher than that of pure AgBrO₃ and g-C₃N₄, respectively. Moreover, the separation and migration efficiency of the photogenerated electron-hole pairs of the as-prepared composites are also enhanced. In addition, superoxide radicals and holes are the dominant active species during the photocatalytic degradation process.

Objectives: Depot medroxyprogesterone acetate (Depo-Provera) is the most commonly used injectable hormone contraceptive in Sub-Saharan Africa where HIV incidence is high. We determined the impact of Depo-Provera on cervical immune cells and mediators in healthy women., Methods: In this longitudinal study, vaginal, endocervical, and rectal swabs were collected at baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) after Depo-Provera injection. Cervical cells were collected by cytobrush and immune markers on cervical CD4 T cells were analyzed by multicolor flow cytometry at three different visits. The levels of immune mediators in cytobrush supernatants as well as vaginal, cervical, and rectal secretions from swabs were analyzed by multiplex assays and ELISA., Results: Compared with baseline levels, we found a significant increase in the frequency of cervical CCR5CD4 T cells and a significant decrease in the frequency of cervical central memory CD4 T cells. Depo-Provera treatment had little effect on expression of immune mediators in rectal mucosa but significantly suppressed numerous immune mediators at cervicovaginal mucosa. Levels of MCP-1, G-CSF, IL-6, IL-10, GM-CSF, and IP-10 were significantly decreased in both vaginal and cervical secretions after Depo-Provera injection. In cervical samples collected by cytobrush, we found reduced levels of 22 of 25 immune mediators after Depo-Provera injection. Changes in immune mediators differed between vaginal and cervical mucosa, demonstrating compartment-specific responses., Conclusion: Depo-Provera altered immune profiles of cervical CD4 T cells and suppressed host immune response at cervicovaginal mucosa, suggesting its likely effect on transmission of sexually transmitted infections including HIV.

Poly(vinyl alcohol) (PVA) hydrogels have been extensively studied as drug delivery systems. However, due to the high hydrophilicity of PVA, these hydrogels have weak abilities to efficiently load drugs and control the initial burst release. In this study, we present a one-step simple and rapid single needle electrospraying (SNESy) method that combines PVA hydrogels with another biocompatible polymer polycaprolactone (PCL). A distinct core-shell structure was obtained with the PVA hydrogel core and PCL shell after the system was properly set up. The results revealed that the volume ratio between PVA hydrogel and PCL played an important role in determining the particle size and the formation of a spherical structure. The double-walled structure of the microsphere was confirmed by taking the fluorescent images and conducting the ATR-FTIR method. Furthermore, doxorubicin hydrochloride was used as a model drug to evaluate the drug loading capacity and the in vitro release behavior of this PVA hydrogel/PCL microsphere. The results indicated that coating a layer of PCL polymer significantly enhanced the drug loading capacity and reduced the drug initial burst release compared to the single-layer PVA hydrogel nanoparticles, demonstrating these biocompatible double-walled microspheres can be applied as excellent drug delivery carriers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rapid thermal cycling (RTC) in an on-chip device can perform DNA amplification in vitro through precise thermal control at each step of the polymerase chain reaction (PCR). This study reports a straightforward fabrication technique for patterning an on-chip graphene-based device with hole arrays, in which the mechanism of surface structures can achieve stable and uniform thermal control for the amplification of DNA fragments. A thin-film based PCR device was fabricated using picosecond laser (PS-laser) ablation of the multilayer graphene (MLG). Under the optimal fluence of 4.72 J/cm 2 with a pulse overlap of 66%, the MLG can be patterned with arrays of 250 μm 2 hole surface structures. A 354-bp DNA fragment of VP1, an effective marker for diagnosing the BK virus, was amplified on an on-chip device in less than 60 min. A thin-film electrode with the aforementioned MLG as the heater was demonstrated to significantly enhance temperature stability for each stage of the thermal cycle. The temperature control of the heater was performed by means of a developed programmable PCR apparatus. Our results demonstrated that the proposed integration of a graphene-based device and a laser-pulse ablation process to form a thin-film PCR device has cost benefits in a small-volume reagent and holds great promise for practical medical use of DNA amplification., (Copyright © 2019. Published by Elsevier B.V.)

Orlistat, an FDA-approved antiobesity drug, has recently been shown to have anticancer effects. However, orlistat is extremely hydrophobic with low absorption. Therefore, new approaches are needed to effectively deliver orlistat for cancer therapy. Herein, we developed a fast and simple method to use polydopamine-coated hollow capsule (PHC) as a drug nanocarrier for enhancing the therapeutic effects of orlistat. Orlistat-loaded PHC had an average size of 200 nm, which was characterized by using dynamic light scattering and scanning electron microscope. Furthermore, the polydopamine layer provided an excellent control of orlistat release because it was extremely sensitive to pH values. The cellular uptake and cytotoxicity experiments were performed to show that orlistat packaged in PHC could be endocytosed into cells and then significantly improved the cytotoxic activity against cancer cell lines in a short time compared with free orlistat. Moreover, dynamic study of cell membrane lysis was performed by staining with the LIVE/DEAD kit to demonstrate the cancer-killing mechanism. The size of the cell surface area has also been proven to be a key parameter which affected drug efficacy. Taken all together, these results present that orlistat-loaded PHC is a very promising formula for cancer treatments.

Highly sensitive long-period fiber gratings (LPFG) was developed for label-free and rapid detection of Staphylococcus aureus (S. aureus). Specifically, the LPFG was functionalized with antibody and nanopitted polyelectrolyte coatings to facilitate bacterial adhesion and thus enhance the sensitivity of bacteria detection. The kinetics of S. aureus adhesion on functional coatings were tracked by surface morphology evolution and time-resolved resonance wavelength shift of the coated LPFG at a flow rate of 30 μl/ml and 37 °C in the concentration range of 10 4 -10 8 colony forming unit (CFU)/ml. S. aureus detection at concentrations as low as 224 CFU/ml can be achieved within a short time span of 30 min. The LPFG-based biosensor can be readily adapted to a variety of biophotonic platforms, for applications such as food safety inspection, environmental monitoring, clinical diagnostics, and medical applications., (Copyright © 2019. Published by Elsevier B.V.)

Antrodia cinnamomea, an endemic fungus species of Taiwan, has long been used as a luxurious dietary supplement to enhance liver functions and as a remedy for various cancers. Antroquinonol (AQ), identified from the mycelium of A. cinnamomea, is currently in phase II clinical trials in the USA and Taiwan for the treatment of non-small-cell lung cancer. In the previous studies, we have demonstrated that AQ and 4-acetylantroquinonol B (4-AAQB) utilize orsellinic acid, via polyketide pathway, as the ring precursor, and their biosynthetic sequences are similar to those of coenzyme Q. In order to test 4-hydroxybenzoic acid (4-HBA), synthesized via shikimate pathway, is the ring precursor of AQ analogs, the strategy of metabolic labeling with stable isotopes was applied in this study. Here we have confirmed that 4-HBA serves as the ring precursor for AQ but not a precursor of 4-AAQB. Experimental results indicated that A. cinnamomea preferentially utilizes endogenous 4-HBA via shikimate pathway for AQ biosynthesis. Exogenous tyrosine and phenylalanine can be utilized for AQ biosynthesis when shikimate pathway is blocked by glyphosate. The benzoquinone ring of 4-AAQB is synthesized only via polyketide pathway, but that of AQ is synthesized via both polyketide pathway and shikimate pathway. The precursor-products relationships diagram of AQ and 4-AAQB in A. cinnamomea are proposed based on the experimental findings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)