Negative regulation of type I interferon signaling by integrin-linked kinase permits dengue virus replication.

Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κB-driven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection.

FOSL1 modulates Schwann cell responses in the wound microenvironment and regulates peripheral nerve regeneration.

Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and contribute to the generation of a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, we find that FOSL1, a AP-1 member that encodes transcription factor FOS Like 1, is highly expressed at the injured sites following peripheral nerve crush. Interfering FOSL1 decreases the proliferation rate and migration ability of Schwann cells, leading to impaired nerve regeneration. Mechanism investigations demonstrate that FOSL1 regulates Schwann cell proliferation and migration by directly binding to the promoter of EPH Receptor B2 (EPHB2) and promoting EPHB2 transcription. Collectively, our findings reveal the essential roles of FOSL1 in regulating the activation of Schwann cells and indicate that FOSL1 can be targeted as a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.

Roles of the transcriptional regulators Fts1, YlNrg1, YlTup1, and YlSsn6 in the repression of the yeast-to-filament transition in the dimorphic yeast Yarrowia lipolytica.

In dimorphic fungi, the yeast-to-filament transition critical for cell survival under nutrient starvation is controlled by both activators and repressors. However, very few filamentation repressors are known. Here we report that, in the dimorphic yeast Yarrowia lipolytica, the conserved transcription factor YlNrg1 plays a minor role whereas Fts1, a newly identified Zn(II)2 Cys6 zinc cluster transcription factor, plays a key role in filamentation repression. FTS1 deletion caused hyperfilamentation whereas Fts1 overexpression drastically reduced filamentation. The expression of FTS1 is downregulated substantially during the yeast-to-filament transition. Transcriptome sequencing revealed that Fts1 represses 401 genes, including the filamentation-activating transcription factor genes MHY1, YlAZF1, and YlWOR4 and key cell wall protein genes. Tup1-Ssn6, a general transcriptional corepressor, is involved in the repression of many cellular functions in fungi. We show that both YlTup1 and YlSsn6 strongly repress filamentation in Y. lipolytica. YlTup1 and YlSsn6 together repress 1383 genes, including a large number of transcription factor and cell wall protein genes, which overlap substantially with Fts1-repressed genes. Fts1 interacts with both YlTup1 and YlSsn6, and LexA-Fts1 fusion represses a lexAop-promoter-lacZ reporter in a Tup1-Ssn6-dependent manner. Our findings suggest that Fts1 functions as a transcriptional repressor, directing the repression of target genes through the Tup1-Ssn6 corepressor.

Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019.

OBJECTIVES: To provide an overview and in-depth analysis of temporal trends in prevalence of musculoskeletal (MSK) disorders in women of childbearing age (WCBA) at global, regional and national levels over the last 30 years, with a special focus on their associations with age, period and birth cohort. METHODS: Estimates and 95% uncertainty intervals (UIs) for MSK disorders prevalence in WCBA were extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. An age-period-cohort model was adopted to estimate the overall annual percentage change of prevalence (net drift, % per year), annual percentage change of prevalence within each age group (local drift, % per year), fitted longitudinal age-specific rates adjusted for period deviations (age effects) and period/cohort relative risks (period/cohort effects) from 1990 to 2019. RESULTS: In 2019, the global number of MSK disorders prevalence in WCBA was 354.57 million (95% UI: 322.64 to 387.68). Fifty countries had at least one million prevalence, with India, China, the USA, Indonesia and Brazil being the highest accounting for 51.03% of global prevalence. From 1990 to 2019, a global net drift of MSK disorders prevalence in WCBA was -0.06% (95% CI: -0.07% to -0.05%) per year, ranging from -0.09% (95% CI: -0.10% to -0.07%) in low-middle sociodemographic index (SDI) region to 0.10% (95% CI: 0.08% to 0.12%) in high-middle SDI region, with 138 countries presenting increasing trends, 24 presenting decreasing trends and 42 presenting relatively flat trends. As reflected by local drift, higher SDI regions had more age groups showing rising prevalence whereas lower SDI regions had more declining prevalence. Globally, an increasing occurrence of MSK disorders prevalence in WCBA beyond adolescent and towards the adult stage has been prominent. Age effects illustrated similar patterns across different SDI regions, with risk increasing with age. High SDI region showed generally lower period risks over time, whereas others showed more unfavourable period risks. High, high-middle and middle SDI regions presented unfavourable prevalence deteriorations, whereas others presented favourable prevalence improvements in successively birth cohorts. CONCLUSIONS: Although a favourable overall temporal trend (net drift) of MSK disorders prevalence in WCBA was observed over the last 30 years globally, there were 138 countries showing unfavourable rising trends, coupled with deteriorations in period/cohort risks in many countries, collectively raising concerns about timely realisation of the Targets of Sustainable Development Goal. Improvements in the MSK disorders-related prevention, management and treatment programmes in WCBA could decline the relative risk for successively younger birth cohorts and for all age groups over period progressing.

Advances in high-resolution mass spectrometry techniques for analysis of high mass-to-charge ions.

A major challenge in modern mass spectrometry (MS) is achieving high mass resolving power and accuracy for precision analyses in high mass-to-charge (m/z) regions. To advance the capability of MS for increasingly demanding applications, understanding limitations of state-of-the-art techniques and their status in applied sciences is essential. This review summarizes important instruments in high-resolution mass spectrometry (HRMS) and related advances to extend their working range to high m/z regions. It starts with an overview of HRMS techniques that provide adequate performance for macromolecular analysis, including Fourier-transform, time-of-flight (TOF), quadrupole-TOF, and related data-processing techniques. Methodologies and applications of HRMS for characterizing macromolecules in biochemistry and material sciences are summarized, such as top-down proteomics, native MS, drug discovery, structural virology, and polymer analyses.

Bmo-miR-6498-5p suppresses Bombyx mori nucleopolyhedrovirus infection by down-regulating BmPLPP2 to modulate pyridoxal phosphate content in B. mori.

The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori-BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.

Streptococcus taonis sp. nov., a novel bacterial species isolated from a blood culture of a patient.

One Gram stain-positive, catalase-negative, α-hemolytic, chain-forming or paired cocci, designated ST22-14T, was isolated from a blood culture of a child with suspected infection. The results of 16S rRNA gene sequences analyses showed that the most closely related species to strain ST22-14T were "Streptococcus vulneris" DM3B3T (99.2%), Streptococcus mitis NCTC 12261T (99.0%), "Streptococcus gwangjuense" ChDC B345T, (99.0%), Streptococcus oralis subsp. dentisani 7747T (99.0%), Streptococcus downii CECT 9732T (99.0%), and Streptococcus infantis ATCC 700779T (98.9%). The genome of strain ST22-14T consists of 2,053,261 bp with a G + C content of 39.4%. Average nucleotide identity values between strain ST22-14T and Streptococcus mitis NCTC 12261T or other five species were from 82.2 to 88.0%. In silico DNA-DNA hybridization of ST22-14T showed an estimated DNA reassociation value of 34.6% with the closest species. The main cellular fatty acids of strain ST22-14T were 16:0, 18:0, 14:0, 18:1ω7c and 18:1ω6c. Based on these results, strain ST22-14T should be classified as a novel species of genus Streptococcus, for which the name Streptococcus taonis sp. nov. is proposed (type strain ST22-14T = NBRC 116002T = BCRC 81402T).

MicroRNAs-associated with FOXO3 in cellular senescence and other stress responses.

FOXO3 is a member of the FOXO transcription factor family and is known for regulating cellular survival in response to stress caused by various external and biological stimuli. FOXO3 decides cell fate by modulating cellular senescence, apoptosis and autophagy by transcriptional regulation of genes involved in DNA damage response and oxidative stress resistance. These cellular processes are tightly regulated physiologically, with FOXO3 acting as the hub that integrates signalling networks controlling them. The activity of FOXO3 is influenced by post-translational modifications, altering its subcellular localisation. In addition, FOXO3 can also be regulated directly or indirectly by microRNAs (miRNAs) or vice versa. This review discusses the involvement of various miRNAs in FOXO3-driven cellular responses such as senescence, apoptosis, autophagy, redox and inflammation defence. Given that these responses are linked and influence cell fate, a thorough understanding of the complex regulation by miRNAs would provide key information for developing therapeutic strategy and avoid unintended consequences caused by off-site targeting of FOXO3.

Multicenter evaluation of the safety and efficacy of selective internal radiation therapy with yttrium-90 resin microspheres in Taiwan: data from the RESIN registry.

BACKGROUND AND AIM: The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. METHODS: Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). RESULTS: Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n = 8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. CONCLUSIONS: Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.

Local symmetry-driven interfacial magnetization and electronic states in (ZnO)n/(w-FeO)n superlattices.

Superlattices constructed with the wide-band-gap semiconductor ZnO and magnetic oxide FeO, both in the wurtzite structure, have been investigated using spin-polarized first-principles calculations. The structural, electronic and magnetic properties of the (ZnO)n/(w-FeO)n superlattices were studied in great detail. Two different interfaces in the (ZnO)n/(w-FeO)n superlattices were identified and they showed very different magnetic and electronic properties. Local symmetry-driven interfacial magnetization and electronic states can arise from different Fe/Zn distributions at different interfaces or spin ordering of Fe in the superlattice. The local symmetry-driven interfacial magnetization and electronic states, originating either from different Fe/Zn distribution across interfaces I and II, or by spin ordering of Fe in the superlattice, can be identified. It was also found that, in the case of the ferromagnetic phase, the electrons are more delocalized for the majority spin but strongly localized for the minority spin, which resulted in interesting spin-dependent transport properties. Our results will pave the way for designing novel spin-dependent electronic devices through the construction of superlattices from semiconductors and multiferroics.

Quinoline, Indole, and Isogranatanine Alkaloids from Malayan Leuconotis eugeniifolia.

Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 µM, respectively.

Reversible Mn2+/Mn4+ double redox in lithium-excess cathode materials.

There is an urgent need for low-cost, resource-friendly, high-energy-density cathode materials for lithium-ion batteries to satisfy the rapidly increasing need for electrical energy storage. To replace the nickel and cobalt, which are limited resources and are associated with safety problems, in current lithium-ion batteries, high-capacity cathodes based on manganese would be particularly desirable owing to the low cost and high abundance of the metal, and the intrinsic stability of the Mn4+ oxidation state. Here we present a strategy of combining high-valent cations and the partial substitution of fluorine for oxygen in a disordered-rocksalt structure to incorporate the reversible Mn2+/Mn4+ double redox couple into lithium-excess cathode materials. The lithium-rich cathodes thus produced have high capacity and energy density. The use of the Mn2+/Mn4+ redox reduces oxygen redox activity, thereby stabilizing the materials, and opens up new opportunities for the design of high-performance manganese-rich cathodes for advanced lithium-ion batteries.

Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial.

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).

Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.

BACKGROUND: The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021. METHODS: We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination. RESULTS: Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement. CONCLUSIONS: Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes.

Bluefin tuna reveal global patterns of mercury pollution and bioavailability in the world's oceans.

Bluefin tuna (BFT), highly prized among consumers, accumulate high levels of mercury (Hg) as neurotoxic methylmercury (MeHg). However, how Hg bioaccumulation varies among globally distributed BFT populations is not understood. Here, we show mercury accumulation rates (MARs) in BFT are highest in the Mediterranean Sea and decrease as North Pacific Ocean > Indian Ocean > North Atlantic Ocean. Moreover, MARs increase in proportion to the concentrations of MeHg in regional seawater and zooplankton, linking MeHg accumulation in BFT to MeHg bioavailability at the base of each subbasin's food web. Observed global patterns correspond to levels of Hg in each ocean subbasin; the Mediterranean, North Pacific, and Indian Oceans are subject to geogenic enrichment and anthropogenic contamination, while the North Atlantic Ocean is less so. MAR in BFT as a global pollution index reflects natural and human sources and global thermohaline circulation.

Serum albumin mediates the associations between heavy metals and two novel systemic inflammation indexes among U.S. adults.

BACKGROUND: The effects of heavy metal exposure on immunological function have sparked widespread concern, but unequivocal evidence on the association between mixed metal exposure and novel systemic inflammatory indexes remains scarce. OBJECTIVES: This study aimed to analyze the associations of heavy metals with two novel systemic inflammation indexes and the mediated effects of serum albumin. METHODS: Nineteen metals were detected among 4082 U.S. adults based on the NHANES. A linear regression, restricted cubic splines (RCS) regression, weighted quantile sum (WQS), Quantile-based Gcomputation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted to evaluate the associations of single metal and mixed metals with systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) levels, respectively. A series of subgroup analyses were used to identify potentially vulnerable populations. Furthermore, we conducted mediation analyses to investigate the mediated effects of serum albumin on the associations of metals with SII and SIRI. RESULTS: In the single-exposure model, exposure to various metals such as urinary Co, As, and serum Zn, Cu was associated with SII and SIRI (PFDR<0.05). Simultaneously, the above metals were linear positively correlated with SII and SIRI. Mixed-exposure analyses consistently showed that overall mixed urinary metal levels were positively pertinent for SII and SIRI levels, and the metal Co played a significant role in the urinary metal mixtures. Subgroup analyses showed that exposure to urinary Cd in men and elderly people increased SII and SIRI levels. The results of mediation analyses suggested the association of urinary metal mixture with SII and SIRI was mediated by albumin, and the proportion of mediation was 14.45% and 9.49%, respectively. CONCLUSIONS: Our findings suggested that metal exposure is strongly associated with the levels of system inflammation indexes and that serum albumin is, in part, a mediator of this association.

Prediction of surgical outcomes in severe encapsulating peritoneal sclerosis using a computed tomography scoring system.

BACKGROUND/PURPOSE: Encapsulating peritoneal sclerosis (EPS) is a rare and potential lethal complication of peritoneal dialysis characterized by bowel obstruction. Surgical enterolysis is the only curative therapy. Currently, there are no tools for predicting postsurgical prognosis. This study aimed to identify a computed tomography (CT) scoring system that could predict mortality after surgery in patients with severe EPS. METHODS: This retrospective study enrolled patients with severe EPS who underwent surgical enterolysis in a tertiary referral medical center. The association of CT score with surgical outcomes including mortality, blood loss, and bowel perforation was analyzed. RESULTS: Thirty-four patients who underwent 37 procedures were recruited and divided into a survivor and non-survivor group. The survivor group had higher body mass indices (BMIs, 18.1 vs. 16.7 kg/m2, p = 0.035) and lower CT scores (11 vs. 17, p < 0.001) than the non-survivor group. The receiver operating characteristic curve revealed that a CT score of ≥15 could be considered a cutoff point to predict surgical mortality, with an area under the curve of 0.93, sensitivity of 88.9%, and specificity of 82.1%. Compared with the group with CT scores of <15, the group with CT scores of ≥15 had a lower BMI (19.7 vs. 16.2 kg/m2, p = 0.004), higher mortality (4.2% vs. 61.5%, p < 0.001), greater blood loss (50 vs. 400 mL, p = 0.007), and higher incidence of bowel perforation (12.5% vs. 61.5%, p = 0.006). CONCLUSION: The CT scoring system could be useful in predicting surgical risk in patients with severe EPS receiving enterolysis.

Combined model integrating deep learning, radiomics, and clinical data to classify lung nodules at chest CT.

OBJECTIVES: The study aimed to develop a combined model that integrates deep learning (DL), radiomics, and clinical data to classify lung nodules into benign or malignant categories, and to further classify lung nodules into different pathological subtypes and Lung Imaging Reporting and Data System (Lung-RADS) scores. MATERIALS AND METHODS: The proposed model was trained, validated, and tested using three datasets: one public dataset, the Lung Nodule Analysis 2016 (LUNA16) Grand challenge dataset (n = 1004), and two private datasets, the Lung Nodule Received Operation (LNOP) dataset (n = 1027) and the Lung Nodule in Health Examination (LNHE) dataset (n = 1525). The proposed model used a stacked ensemble model by employing a machine learning (ML) approach with an AutoGluon-Tabular classifier. The input variables were modified 3D convolutional neural network (CNN) features, radiomics features, and clinical features. Three classification tasks were performed: Task 1: Classification of lung nodules into benign or malignant in the LUNA16 dataset; Task 2: Classification of lung nodules into different pathological subtypes; and Task 3: Classification of Lung-RADS score. Classification performance was determined based on accuracy, recall, precision, and F1-score. Ten-fold cross-validation was applied to each task. RESULTS: The proposed model achieved high accuracy in classifying lung nodules into benign or malignant categories in LUNA 16 with an accuracy of 92.8%, as well as in classifying lung nodules into different pathological subtypes with an F1-score of 75.5% and Lung-RADS scores with an F1-score of 80.4%. CONCLUSION: Our proposed model provides an accurate classification of lung nodules based on the benign/malignant, different pathological subtypes, and Lung-RADS system.

The increased lateral tibial slope may result in inferior long-term clinical outcome after DB-ACL reconstruction.

PURPOSE: To determine if there is a correlation between lateral tibial slope and long-term clinical results in patients who underwent double-bundle ACL reconstruction. METHODS: We retrospectively reviewed patients that received double-bundle ACL reconstruction at a single institution by a single surgeon from January 2011 to December 2014. All the magnetic resonance imaging were reviewed and lateral tibial slopes (LTS) were recorded by an experienced surgeon and rechecked by the other two authors of this study that specialized in orthopedic knee surgery. The relationship between PROMs measurement and lateral tibial slope were analyzed. The patients were then separated into two groups (LTS > 7.4° and < 7.4°) according to the previous study. RESULTS: A total of 119 patients were enrolled in this study. All enrolled patients were followed for at least 8 years. The PROMS result were negatively correlated with the lateral tibial slope (p values all < 0.001). The patients with high lateral tibial slope had significantly lower PROMS values (Lysholm 94.26 ± 5.61 vs 80.15 ± 8.28, p = 0.013; IKDC 82.99 ± 4.55 vs 70.09 ± 7.15, p = 0.003; Tegner 9.32 ± 0.95 vs 6.85 ± 1.99, p < 0.001). Finally, the LTS cutoff value between patients with "Good" and "Fair" Lysholm score in our study was 7.55 degrees. CONCLUSIONS: Patients with high lateral tibial slope may result in inferior long-term subjective outcomes. The using of double-bundle ACL reconstruction along cannot overcome the negative impact caused by steep lateral tibial slope. A lateral tibial slope of 7.55° may be used as a cut-off for a good clinical outcome. LEVEL OF EVIDENCE: III retrospective comparative prognostic trial.

miR-140 and miR-200 regulate the migratory heterogeneity of location-specific Schwann cell population.

Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR-140 and miR-200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR-140 and miR-200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine.