IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.

An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-ß activity through its receptor stability in dermal fibroblasts.

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.

Hurricane annual cycle controlled by both seeds and genesis probability.

Understanding tropical cyclone (TC) climatology is a problem of profound societal significance and deep scientific interest. The annual cycle is the biggest radiatively forced signal in TC variability, presenting a key test of our understanding and modeling of TC activity. TCs over the North Atlantic (NA) basin, which are usually called hurricanes, have a sharp peak in the annual cycle, with more than half concentrated in only 3 mo (August to October), yet existing theories of TC genesis often predict a much smoother cycle. Here we apply a framework originally developed to study TC response to climate change in which TC genesis is determined by both the number of pre-TC synoptic disturbances (TC "seeds") and the probability of TC genesis from the seeds. The combination of seeds and probability predicts a more consistent hurricane annual cycle, reproducing the compact season, as well as the abrupt increase from July to August in the NA across observations and climate models. The seeds-probability TC genesis framework also successfully captures TC annual cycles in different basins. The concise representation of the climate sensitivity of TCs from the annual cycle to climate change indicates that the framework captures the essential elements of the TC climate connection.

Improvement in swallowing safety after injection laryngoplasty in patients with unilateral vocal paralysis complicated with aspiration.

BACKGROUND: The benefit of injection laryngoplasty (IL) on voice for unilateral vocal fold paralysis (UVFP) is supported increasingly in literatures, yet less is known for swallowing. Also, prevalence of patient-reported dysphagia is substantially higher than instrumental studies. This prospective study focused on swallowing outcomes, with predetermined flexible endoscopic evaluation of swallowing (FEES) protocol that simulates daily life situation. METHODS: Adult patients with UVFP and aspiration receiving IL were recruited. Voice outcome measurements, as well as swallowing outcomes including Eating Assessment Tool (EAT-10) and FEES, which challenged patients with different fluid volumes: 10 mL, 20 mL, and 90 mL cup sipping were evaluated. RESULTS: Significant improvements were demonstrated in all voice outcomes. Significant changes were also presented inEAT-10 (P < 0.01). Pre-operatively, penetration-aspiration scale (PAS) was 1.5 ± 1.3, 1.9 ± 1.7 and 2.3 ± 1.8 for 10 mL, 20 mL and 90 mL serial sipping, and improved to 1.1 ± 0.3, 1.1 ± 0.4 and 1.4 ± 0.7 post-operatively (P < 0.01). Safe swallowing (PAS ≤ 2) was achieved in all, except for one patient, who presented with a post-injection PAS of 4 (material enters the airway, contacts the vocal folds, and is ejected from the airway) on 90 mL cup sipping, whose pre-injection PAS was 7 (residue in trachea). CONCLUSION: Maintaining swallowing function suitable for social environment is important. Our results demonstrated the feasibility of the predetermined FEES protocol, and positive effects of IL on both voice and swallowing outcomes.

Potential natural product 3,4-seco-schitriterpenoids from Kadsura japonica L. as anti-neuroinflammatory agents.

In the present study, the undescribed schitriterpenoids, kadsujanonols A-I (1-9), and eleven reported compounds (10-20) were isolated from K. japonica L. vines. Their structures of 3,4-seco-schitriterpenoids were elucidated mainly by spectroscopic analyses including 1H-, 13C-, and 2D-NMR, IR, HRESIMS spectra. The spatial configurations were determined by the single-crystal X-ray diffraction analysis of kadsujapnonol A (1), 15, 17, and 18, CD data and computational analysis. Furthermore, all isolates were evaluated for the anti-neuroinflammatory activity on LPS-stimulated NO production in BV2 microglial cells and compounds 2, 4, 5, 7, 9, 11, 13-16, and 18 exposed better or comparable suppression abilities than PDTC. Among them, kadlongilactone B (14) showed the best significant inhibiting ability (IC50 = 0.87 µg/mL) and the effect is through the attenuation of the inflammatory transcription factor p65NF-κB. Preliminary structure-activity relationship revealed that δ-lactone at the side chain and 7-member lactone at C-3/C-4, and 3,4:9,10 ring opening are important.

Spatial variant gloss measurement of dielectric materials based on a polarized camera.

This study proposes an imaging method for gloss measurement solely by a single shot from a polarized camera. The system, comprising a polarized camera and well-diffused LED plate light, is inspired by the framework of ASTM D523, and it acquires images at 60° incident direction. The polarization characteristics of dielectric material samples were analyzed. A regression model was developed by using natural color system gloss scale and a commercial gloss meter. Subsequently, the gloss and spatial resolutions of this method were verified using various types of measurement samples. From experiments regarding different benchmarks, we concluded that the proposed method performs sufficiently for spatial variant gloss measurement.

Nipple-areolar complex (NAC) or skin flap ischemia necrosis post nipple-sparing mastectomy (NSM)-analysis of clinicopathologic factors and breast magnetic resonance imaging (MRI) features.

BACKGROUND: The purpose of this study is to identify clinicopathologic factors and/or preoperative MRI vascular patterns in the prediction of ischemia necrosis of the nipple-areola complex (NAC) or skin flap post nipple-sparing mastectomy (NSM). METHODS: We performed a retrospective analysis of 441 NSM procedures from January 2011 to September 2021 from the breast cancer database at our institution. The ischemia necrosis of NAC or skin flap was evaluated in correlation with clinicopathologic factors and types of skin incision. Patients who received NSM with preoperative MRI evaluation were further evaluated for the relationship between vascular pattern and the impact on ischemia necrosis of NAC or skin flap. RESULTS: A total of 441 cases with NSM were enrolled in the current study, and the mean age of the cases was 49.1 ± 9.8 years old. A total of 41 (9.3%) NSM procedures were found to have NAC ischemia/necrosis. Risk factors were evaluated of which old age, large mastectomy specimen weight (> 450 g), and peri-areola incision were identified as predictors of NAC necrosis. Two-hundred seventy NSM procedures also received preoperative MRI, and the blood supply pattern was 18% single-vessel type and 82% double-vessel pattern. There were no correlations between MRI blood supply patterns or types of skin flap incisions with ischemia necrosis of NAC. There were also no correlations between blood loss and the pattern or size of the blood vessel. CONCLUSION: Factors such as the type of skin incision, age, and size of mastectomy weight played an important role in determining ischemia necrosis of NAC; however, MRI vascular (single or dual vessel supply) pattern was not a significant predictive factor.

Proactive Swallowing Rehabilitation in Patients with Recurrent Oral Cancer Receiving Salvage Treatment: Long-Term Swallowing-Related Outcomes.

The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life in patients with recurrent oral cancer in the first 2 years after salvage treatment. Consecutive adult patients with recurrent oral cancer who received salvage surgery and free flap reconstruction were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, 18 and 24 months were evaluated. A total of 50 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in BW and FOIS from one month, and in MDADI from three months. All patients were free of tube feeding at 18-24 months and tolerated diet with special preparations or compensation. Safe swallowing could be achieved in approximately 80% participants after 12 months of diet modification or compensatory maneuvers. Proactive swallowing therapy was feasible in patients with recurrent oral cancer receiving salvage treatment. Although this patient population might have pre-existing dysphagia from previous treatments, rehabilitation could facilitate safe per oral intake and maintain adequate nutrition with adaptive maneuvers or compensatory strategies. Patients who underwent proactive swallowing rehabilitation had better recovery in the functional oral intake level.

Histology-based and cytology-based needle sampling for targeted next-generation sequencing in the indeterminate thyroid tumors.

PURPOSE: To establish the optimal and minimally invasive diagnostic approach for targeted next-generation sequencing (NGS) in the indeterminate thyroid tumors. METHODS: The patients with indeterminate thyroid tumors were prospectively recruited and analyzed in a single tertiary medical center. We performed FNA and core needle biopsy (CNB) at the surgical specimens to confirm the quality of each sampling procedure. Cytological diagnosis by FNA, histological diagnosis by CNB and confirmed diagnosis by final surgery were compared to demonstrate the agreement among these approaches for the indeterminate thyroid tumors. The quality of the samples from FNA and CNB was evaluated, respectively to determine the optimal approach for targeted NGS. Finally, we performed ultrasound-guided CNB and FNA (US-CNB and US-FNA) on one case to confirm the clinical feasibility of being a pre-operative minimally invasive diagnostic approach. RESULTS: A total of 6 female patients (average age: 50.83 ± 15.18 years) with indeterminate thyroid tumors (average size: 1.79 ± 0.91 cm) were recruited for further analyses. The pathological diagnoses could be obtained by CNB in the first five cases, and the sample quality of CNB for targeted NGS was better than that of FNA, even after 10X dilution. The gene mutations associated with thyroid malignancy could be detected by NGS. In the case treated with US-CNB, the pathological and targeted NGS results were successfully obtained, which suggested the possibility of thyroid malignancy to facilitate immediate decision of subsequent treatment. CONCLUSION: CNB could serve as a minimally invasive diagnostic approach in the indeterminate thyroid tumors by providing pathological diagnoses and qualified samples for detection of mutated genes, which facilitates appropriate and immediate management.

Effects of surgery on the relationship between subglottic pressure and fundamental frequency in vocal fold dynamics in patients with benign laryngeal diseases.

PURPOSE: Subglottic pressure (Ps) and fundamental frequency (F0) play important roles in governing vocal fold (VF) dynamics. Theoretical description, model simulation, excised larynx and animal models have been used in previous studies, yet clinically applicable measurements are still lacking. This study aimed to evaluate the effects of surgery for benign laryngeal lesions by investigating the relationship between F0 and Ps. METHODS: Patients with benign laryngeal lesions who underwent phonosurgery were prospectively recruited. Participants were instructed to sustain voicing the vowel /o/ at three incremental frequencies four semitones apart in the modal register (F01, F02, F03). F0 was estimated by VF vibration on the accelerometer. Ps change was achieved and measured using the airflow interruption method. RESULTS: Thirteen patients with a mean age (SD) of 43.5 (12.4) years were included. The change in F0 per unit change of Ps, which is the slope (Hz/kPa) of the regression line of the frequency-pressure data pairs, decreased as the tension of the VF increased. The slopes significantly increased after the operation for F01 and F02 (36.43 ± 14.68 preoperatively, 53.91 ± 30.71 postoperatively, p = 0.011 and 26.02 ± 10.71; 34.85 ± 17.92, p = 0.046, respectively). In addition, there was a significant decrease in phonation threshold pressure and improvements in the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap inventory-10. CONCLUSIONS: The relationship between F0 and Ps may serve as an objective assessment of the outcomes in the treatment of benign laryngeal diseases with clinical relevance.

Incorporation of ultrasound-guided core biopsy with flow cytometry to assist the diagnosis of cervical lymphoma.

PURPOSE: The main purpose of surgery for cervical lymphoma is only for tissue sampling. To establish a patient-friendly diagnostic approach, we investigated the feasibility of ultrasound-guided core biopsy with flow cytometry in the patients with suspected cervical lymphoma. METHODS: We prospectively recruited patients with suspected cervical lymphoma from Nov 2017 till Jan 2021 in a referral medical center and performed retrospective interpretation of the prospectively acquired data. Ultrasound-guided core biopsy as the tissue sampling approach for the targeted lesions was performed in all patients. The ultrasound-guided core biopsy samples were analyzed by immunohistochemical stains and flow cytometry. The sample quality and the rate of definite and decisive diagnosis obtained by ultrasound-guided core biopsy alone and ultrasound-guided core biopsy with flow cytometry were evaluated. RESULTS: Total 81 consecutive patients were recruited for analysis. All ultrasound-guided core biopsy samples were qualified for analysis of pathology and flow cytometry. Pathologically, the diagnoses were definite and compatible with their flow cytometry results in 70 patients (86.42%). Either newly-diagnosed or recurrent cervical lymphoma/lymphoproliferative disorders with histologic transformation could be diagnosed by ultrasound-guided core biopsy with flow cytometry. Nine of the 11 patients with pathologically indefinite diagnosis became clinically decisive when flow cytometry was incorporated into the process, which improved the rate of decisive diagnosis to 98.77% (Odds ratio [95% CI]: 6.21 [1.28, 58.96]). CONCLUSION: Ultrasound-guided core biopsy combined with flow cytometry is suggested to serve as the first-line and patient-friendly diagnostic approach for the patients with suspected cervical lymphoma.

Application of ultrasound in distinguishing the incipient microtumor from inherent lymph nodes of the parotid glands.

BACKGROUND: Parotid microtumors (size ≤ 1 cm) pose a significant clinical challenge due to their malignant potential and risks associated with surgery. It is imperative to explore the diagnostic workflow that incorporates ultrasound (US) in order to make appropriate clinical decisions with minimal invasiveness. METHODS: The patients receiving both US and ultrasound-guided fine needle aspiration (USFNA) for the parotid microtumors in a medical center were retrospectively recruited. The ultrasonic features, cytology of USFNA, and final surgical pathology were analyzed to differentiate the tumor origins and their malignant potential. RESULTS: From August 2009 to March 2016, a total of 92 patients were enrolled in the study. The short axis, long-to-short axis ratio, and presence of an echogenic hilum were found to be significantly useful in distinguishing lymphoid tissue origin from salivary gland origin, which was confirmed by USFNA. An irregular border was predictive for malignant parotid microtumors from both origins. Intra-tumoral heterogeneity was also identified as a significant feature associated with malignant lymph nodes. USFNA was able to confirm all malignant lymph nodes, but it had a false negative rate of 8.5% in parotid microtumors of salivary gland origin. Based on the analysis of US and USFNA results, a diagnostic workflow for parotid microtumors was proposed. CONCLUSION: US and USFNA can be helpful in classifying the origins of parotid microtumors. US-FNA carries the risk of producing false negative results specifically for microtumors originating from salivary glands, but not lymphoid tissue. The diagnostic workflow, which incorporates both US and USFNA, assists in determining the clinical decision for diagnosing and managing parotid microtumors.

Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress.

Aortic wall inflammation, abnormal oxidative stress and progressive degradation of extracellular matrix proteins are the main characteristics of abdominal aortic aneurysms (AAAs). The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation plays a crucial role in aortic damage and disease progression. The first aim of this study was to examine the effect of baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in apolipoprotein E-deficient (ApoE-/-) mice. The second aim was to define whether baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation and inflammation in VSMC culture. For male ApoE-/- mice, a clinically relevant AAA model was randomly divided into four groups: saline infusion, baicalein intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, preserved elastic structure and density and prevented smooth muscle cell contractile protein degradation. Baicalein inhibited rat VSMC proliferation and migration following the stimulation of VSMC cultures with Ang II while blocking the Ang II-inducible cell cycle progression from G0/G1 to the S phase in the synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated that baicalein inhibited the expression of PCNA and significantly lowered levels of phospho-Akt and phospho-ERK, along with an increase in baicalein concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its reactive oxygen species (ROS) production decreased, along with the baicalein pretreatment. Our overall results indicate that baicalein could have therapeutic potential in preventing aneurysm development.

Chondrocyte Thrombomodulin Protects against Osteoarthritis.

Osteoarthritis (OA) is a prevalent form of arthritis that affects over 32.5 million adults worldwide, causing significant cartilage damage and disability. Unfortunately, there are currently no effective treatments for OA, highlighting the need for novel therapeutic approaches. Thrombomodulin (TM), a glycoprotein expressed by chondrocytes and other cell types, has an unknown role in OA. Here, we investigated the function of TM in chondrocytes and OA using various methods, including recombinant TM (rTM), transgenic mice lacking the TM lectin-like domain (TMLeD/LeD), and a microRNA (miRNA) antagomir that increased TM expression. Results showed that chondrocyte-expressed TM and soluble TM [sTM, like recombinant TM domain 1 to 3 (rTMD123)] enhanced cell growth and migration, blocked interleukin-1ß (IL-1ß)-mediated signaling and protected against knee function and bone integrity loss in an anterior cruciate ligament transection (ACLT)-induced mouse model of OA. Conversely, TMLeD/LeD mice exhibited accelerated knee function loss, while treatment with rTMD123 protected against cartilage loss even one-week post-surgery. The administration of an miRNA antagomir (miR-up-TM) also increased TM expression and protected against cartilage damage in the OA model. These findings suggested that chondrocyte TM plays a crucial role in counteracting OA, and miR-up-TM may represent a promising therapeutic approach to protect against cartilage-related disorders.

Clinical Updates on Antiplatelet Therapy for Secondary Prevention in Acute Ischemic Stroke.

Antiplatelet therapy is the first-line management for noncardioembolic transient ischemic attack (TIA) and acute ischemic stroke (IS). Herein, we review the safety and efficacy of antiplatelet therapies in patients with IS and TIA, primarily focusing on the acute stage. We discuss current antiplatelet monotherapy and the factors influencing efficacy and continuation rate according to clinical trial data. Aspirin remains the most commonly used first-line antiplatelet agent for preventing noncardioembolic stroke recurrence, and clopidogrel, cilostazol, and ticagrelor are feasible alternatives. Various short-term dual antiplatelet therapies (including clopidogrel-aspirin and ticagrelor-aspirin combination therapy) for minor stroke and high-risk TIA are also reviewed. For selected patients with specific stroke etiologies, short-term dual antiplatelet therapy with aspirin combined with clopidogrel or ticagrelor can significantly reduce the risk of stroke. However, insufficient evidence supports the benefits of triple antiplatelet therapy for recurrent noncardioembolic stroke prevention, and this treatment substantially increases the rate of bleeding complications. Keyword: antiplatelet therapy, acute ischemic stroke, secondary prevention, transient ischemic attack.

Effect of Polarized Training on Cardiorespiratory Fitness of Untrained Healthy Young Adults: A Randomized Control Trial with Equal Training Impulse.

To explore the effects of 8-week polarized training (POL), high-intensity interval training (HIIT), and threshold training (THR) interventions on the cardiorespiratory fitness (CRF) of untrained healthy young adults. This study recruited 36 young adults and randomly assigned them to POL, HIIT, THR, or control (CG) groups to undergo an 8-week training intervention. The training impulse applied to all three intervention groups was identical. The training intensity was divided into Zone 1, 2, and 3 (Z1, Z2 and Z3) on the basis of the ventilatory thresholds (VT). The weekly training intensity distribution for POL was 75% of Z1 and 25% of Z3; HIIT was 100% of Z3 and THR was 50% of Z1 and 50% of Z2. Each group underwent Bruce protocol testing and supramaximal testing before, during, and after the intervention; relevant CRF parameters were assessed. 8 weeks of POL and HIIT significantly increased VT2 (p < 0.05); 8 weeks of POL, HIIT, THR and significantly increased VO2max and TTE (p < 0.05). The effect size of POL in relation to VO2max and TTE improvements was greater than that of HIIT and THR (g = 2.67 vs. 1.26 and 1.49; g = 2.75 vs. 2.05 and 1.60). Aerobic training models with different intensity distributions have different time effects on improving CRF. Relative to HIIT and THR, POL improved more variables of CRF. Therefore, POL is a feasible aerobic training method for improving CRF.

Genetic and Biochemical Characterization of Halogenation and Drug Transportation Genes Encoded in the Albofungin Biosynthetic Gene Cluster.

Albofungin, a hexacyclic aromatic natural product, exhibits broad-spectrum antimicrobial activity. Its biosynthesis, regulation, and resistance remain elusive. Here, we report the albofungin (abf) biosynthetic gene cluster (BGC) from its producing strain Streptomyces tumemacerans JCM5050. The nascent abf BGC encodes 70 putative genes, including regulators, transporters, type II polyketide synthases (PKSs), oxidoreductase, and tailoring enzymes. To validate the intactness and functionality of the BGC, we developed an Escherichia coli-Streptomyces shuttle bacterial artificial chromosome system, whereby the abf BGC was integrated into the genome of a nonproducing host via heterologous conjugation, wherefrom albofungin can be produced, confirming that the BGC is in effect. We then delimited the boundaries of the BGC by means of in vitro CRISPR-Cas9 DNA editing, concluding a minimal but essential 60-kb abf BGC ranging from orfL to abf58. The orfA gene encoding a reduced flavin adenine dinucleotide (FADH2)-dependent halogenase was examined and is capable of transforming albofungin to halogen-substituted congeners in vivo and in vitro. The orfL gene encoding a transporter was examined in vivo. The presence/absence of orfA or orfL demonstrated that the MIC of albofungin is subject to alteration when an extracellular polysaccharide intercellular adhesin was formed. Despite that halogenation of albofungin somewhat increases binding affinity to transglycosylase (TGase), albofungin with/without a halogen substituent manifests similar in vitro antimicrobial activity. Halogenation, however, limits overall dissemination and effectiveness given a high secretion rate, weak membrane permeability, and high hydrophobicity of the resulting products, whereby the functions of orfA and orfL are correlated with drug detoxification/resistance for the first time. IMPORTANCE Albofungin, a natural product produced from Streptomycetes, exhibits bioactivities against bacteria, fungi, and tumor cells. The biosynthetic logic, regulations, and resistance of albofungin remain yet to be addressed. Herein, the minimal albofungin (abf) biosynthetic gene cluster (BGC) from the producing strain Streptomyces tumemacerans JCM5050 was precisely delimited using the Escherichia coli-Streptomyces shuttle bacterial artificial chromosome system, of which the gene essentiality was established in vivo and in vitro. Next, we characterized two genes orfA and orfL encoded in the abf BGC, which act as a reduced flavin adenine dinucleotide (FADH2)-dependent halogenase and an albofungin-congeners transporter, respectively. While each testing microorganism exhibited different sensitivities to albofungins, the MIC values of albofungins against testing strains with/without orfA and/or orfL were subject to considerable changes. Halogen-substituted albofungins mediated by OrfA manifested overall compromised dissemination and effectiveness, revealing for the first time that two functionally distinct proteins OrfA and OrfL are associated together, exerting a novel "belt and braces" mechanism in antimicrobial detoxification/resistance.

The efficacy of incorporating ultrasound-guided core biopsy into the clinical workflow of indeterminate thyroid tumors.

BACKGROUND: Ultrasound-guided core biopsy (USCB) is a minimally invasive sampling procedure which may help to confirm the diagnoses of the thyroid tumors with indeterminate results of ultrasound-guided fine-needle aspiration (USFNA). Although with potential advantages, the working protocol of introducing USCB in the routine practice has not been established yet. This study aims to evaluate the efficacy of USCB when it is included in the clinical workflow of assessing the thyroid tumors with indeterminate USFNA results after a long-term follow up. METHODS: Between 2009 and 2016, consecutive patients receiving thyroid USFNA were reviewed retrospectively in the tertiary referral hospital. The patients, who finally received USCB for their thyroid tumors after repeated indeterminate USFNA results, were recruited. The important sonographic features in facilitating specific diagnoses by USCB, differentiating malignancy from benignity, and confirming origins of thyroid tumors were analyzed and the role of USCB was investigated. RESULTS: Thirty-nine patients met the inclusion criteria were analyzed. The specific diagnoses were confirmed in 23 patients (59%) by USCB. Taller than wide, ill-defined margin and hypoechogenicity helped in differentiating malignant tumors and the latter two features were pertinent to the success of applying USCB for specific diagnosis. No sonographic features were able to differentiate the thyroid malignancy from extra-thyroid origins exclusively. Thyroid USCB facilitated clinical decision making in 37 of the 39 patients (94.9%) with indeterminate USFNA results. CONCLUSION: The USCB is a cost-effective sampling procedure for confirming the diagnosis of indeterminate thyroid tumors and their clinical management, especially for those malignancies from extra-thyroid origins.

An alternative surgical technique for advanced tongue/tongue base cancer without free flap reconstruction.

BACKGROUND/PURPOSE: Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function. METHODS: From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited. RESULTS: The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation. CONCLUSION: Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals.

Performance of High Efficiency Avalanche Poly-SiGe Devices for Photo-Sensing Applications.

This paper explores poly-silicon-germanium (poly-SiGe) avalanche photo-sensors (APSs) involving a device of heterojunction structures. A low pressure chemical vapor deposition (LPCVD) technique was used to deposit epitaxial poly-SiGe thin films. The thin films were subjected to annealing after the deposition. Our research shows that the most optimal thin films can be obtained at 800 °C for 30 min annealing in the hydrogen atmosphere. Under a 3-µW/cm2 incident light (with a wavelength of 550 nm) and up to 27-V biased voltage, the APS with a n+-n-p-p+ alloy/SiO2/Si-substrate structure using the better annealed poly-SiGe film process showed improved performance by nearly 70%, 96% in responsivity, and 85% in quantum efficiency, when compared to the non-annealed APS. The optimal avalanche multiplication factor curve of the APS developed under the exponent of n = 3 condition can be improved with an increase in uniformity corresponding to the APS-junction voltage. This finding is promising and can be adopted in future photo-sensing and optical communication applications.