Application of Carbon Nanoparticles in Transoral Endoscopic Thyroidectomy Vestibular Approach for Unilateral Papillary Thyroid Cancer.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied technology. Carbon nanoparticles (CNs) are novel lymph node tracers that have been widely used in China to help remove central lymph nodes (CLNs) and protect the parathyroid glands (PGs) in open thyroid cancer surgery. This study is to evaluate the effectiveness and safety of CNs in TOETVA. MATERIALS AND METHODS: A total of 158 patients who underwent TOETVA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The participants were divided into a CNs group (n=88) and a control group (n=70), based on whether they received a intraoperative injection of CNs or not. Meanwhile, the CNs group were additionally divided into 2 subgroups, leakage subgroup (n=26) and standard subgroup (n=62). The 2 groups and subgroups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: All common metrics had no significant differences were found between the CNs group and the control group (P>0.05). The standard subgroup of CNs group had advantage over the control group on PGs identification (59/62 vs. 59/70 for superior PG, 56/62 vs. 52/70 for inferior PG, P<0.05). Moreover, the standard subgroup harvested more CLNs than the control group (8.97±2.96 vs. 7.47±2.93, P<0.05). More operation time was spent on the leakage subgroup of CNs group than the control group (160.00±17.61 vs. 140.00±13.32, P<0.05). Meanwhile, the leakage subgroup had disadvantage on intraoperative hemorrhage (26.15±10.80 vs. 21.21±7.09, P<0.05) and hospital durations (4.96±0.72 vs. 4.57±0.69, P<0.05). Furthermore, the leakage group identified fewer inferior PG than the control group (7/26 vs. 52/70, P<0.05). Contrary to the standard subgroup, the CLNs of the leakage subgroup was also unsatisfactory compared with the control group (4.96±1.84 vs. 7.47±2.93, P<0.05). CONCLUSIONS: The application of CNs suspension tracing technology has a definite effect in TOETVA. It can improve the thoroughness of lymph node dissection in the central region and enhance recognition of the PG. However, refined extracapsular anatomy is indispensable to prevent CN leakage. Leaked CNs will also be counterproductive to the operation.

TIPE1 limits virus replication by disrupting PKM2/ HIF-1α/ glycolysis feedback loop.

OBJECTIVE: Virus infection is a major threat to human health and remains a significant cause of death to date. Macrophages are important innate immune cells that exhibit indispensable roles in controlling virus replication. It was recently reported that metabolic adaption determines the functional state of macrophages. Thus, to further unravel the crucial factors involving in metabolic adaption of macrophages might provide the potential candidates for optimizing their anti-viral capabilities. METHODS: RT-PCR, Western blotting, virus plaque assay and HE were used to evaluate the viral load in virus-infected Tipe1M-KO and Tipe1f/f mice or cultured macrophages. RNA sequencing were performed with Tipe1M-KOor Tipe1f/f BMDMs upon virus infection. Extracellular acidification rate (ECAR) was applied for analyzing glycolysis rate in virus-infected BMDMs. Co-immunoprecipitation (Co-IP) assay and LC-MS/MS were used to determine the potential interacting proteins of TIPE1. RESULTS: TIPE1 level was significantly reduced in BMDMs infected with either RNA viruses or DNA virus. Deficiency of Tipe1 in macrophages increased viral load and aggravated tissue damage. Mechanistically, TIPE1 suppressed the glycolytic capacity of macrophages through interacting with PKM2 and promoting its ubiquitination degradation, which in turn decreased HIF1α transcription and viral replication in macrophages. CONCLUSIONS: TIPE1 functions as a novel regulator for metabolic reprogramming and virus infection in macrophages.

Visual interpretable MRI fine grading of meniscus injury for intelligent assisted diagnosis and treatment.

Meniscal injury represents a common type of knee injury, accounting for over 50% of all knee injuries. The clinical diagnosis and treatment of meniscal injury heavily rely on magnetic resonance imaging (MRI). However, accurately diagnosing the meniscus from a comprehensive knee MRI is challenging due to its limited and weak signal, significantly impeding the precise grading of meniscal injuries. In this study, a visual interpretable fine grading (VIFG) diagnosis model has been developed to facilitate intelligent and quantified grading of meniscal injuries. Leveraging a multilevel transfer learning framework, it extracts comprehensive features and incorporates an attributional attention module to precisely locate the injured positions. Moreover, the attention-enhancing feedback module effectively concentrates on and distinguishes regions with similar grades of injury. The proposed method underwent validation on FastMRI_Knee and Xijing_Knee dataset, achieving mean grading accuracies of 0.8631 and 0.8502, surpassing the state-of-the-art grading methods notably in error-prone Grade 1 and Grade 2 cases. Additionally, the visually interpretable heatmaps generated by VIFG provide accurate depictions of actual or potential meniscus injury areas beyond human visual capability. Building upon this, a novel fine grading criterion was introduced for subtypes of meniscal injury, further classifying Grade 2 into 2a, 2b, and 2c, aligning with the anatomical knowledge of meniscal blood supply. It can provide enhanced injury-specific details, facilitating the development of more precise surgical strategies. The efficacy of this subtype classification was evidenced in 20 arthroscopic cases, underscoring the potential enhancement brought by intelligent-assisted diagnosis and treatment for meniscal injuries.

The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation.

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

Therapeutic Effects of a Novel Aptamer on Coronaviral Infection-Induced Lung Injury and Systemic Inflammatory Responses.

BACKGROUND: Coronaviral infection-induced acute lung injury has become a major threat to public health, especially through the ongoing pandemic of COVID-19. Apta-1 is a newly discovered Aptamer that has anti-inflammatory effects on systemic septic responses. The therapeutic effects of Apta-1 on coronaviral infection-induced acute lung injury and systemic responses were evaluated in the present study. METHODS: Female A/J mice (at 12-14 weeks of age) were challenged with murine hepatitis virus 1 (MHV-1), a coronavirus, at 5000 PFU intranasally, followed by Apta-1 intravenously administered (100 mg/kg, twice) 1.5 h or 2 days after viral delivery. Animals were sacrificed at Day 2 or Day 4. Lung tissues were examined with H&E, immunohistochemistry staining, and western blotting. RT-qPCR was used for cytokine gene expression. Serum and plasma were collected for laboratory assessments. RESULTS: Apta-1 treatment reduced viral titers, prevented MHV-1-induced reduction of circulating blood volume and hemolysis, reduced alveolar space hemorrhage, and protease-activated receptor 1 (PAR-1) cleavage. Apta-1 treatment also significantly reduced chemokine (MKC, MCP-1, and RANTES) levels, as well as AST, ALT, total bilirubin, and reduced unconjugated bilirubin levels in the serum. CONCLUSION: Apta-1 showed therapeutic benefits in coronaviral infection-induced hemorrhage and PAR-1 cleavage in the lung. It also has anti-inflammatory effects systemically.

Genomic full-length sequence of the HLA-B*49:11 allele was identified in a Chinese bone marrow donor.

The genomic full-length sequence of HLA-B*49:11 was identified by a group-specific sequencing approach from China.

RtNAC055 promotes drought tolerance via a stomatal closure pathway linked to methyl jasmonate/hydrogen peroxide signaling in Reaumuria trigyna.

The stomata regulate CO2 uptake and efficient water usage, thereby promoting drought stress tolerance. NAC proteins (NAM, ATAF1/2, and CUC2) participate in plant reactions following drought stress, but the molecular mechanisms underlying NAC-mediated regulation of stomatal movement are unclear. In this study, a novel NAC gene from Reaumuria trigyna, RtNAC055, was found to enhance drought tolerance via a stomatal closure pathway. It was regulated by RtMYC2 and integrated with jasmonic acid signaling and was predominantly expressed in stomata and root. The suppression of RtNAC055 could improve jasmonic acid and H2O2 production and increase the drought tolerance of transgenic R. trigyna callus. Ectopic expression of RtNAC055 in the Arabidopsis atnac055 mutant rescued its drought-sensitive phenotype by decreasing stomatal aperture. Under drought stress, overexpression of RtNAC055 in poplar promoted ROS (H2O2) accumulation in stomata, which accelerated stomatal closure and maintained a high photosynthetic rate. Drought upregulated the expression of PtRbohD/F, PtP5CS2, and PtDREB1.1, as well as antioxidant enzyme activities in heterologous expression poplars. RtNAC055 promoted H2O2 production in guard cells by directly binding to the promoter of RtRbohE, thus regulating stomatal closure. The stress-related genes RtDREB1.1/P5CS1 were directly regulated by RtNAC055. These results indicate that RtNAC055 regulates stomatal closure by maintaining the balance between the antioxidant system and H2O2 level, reducing the transpiration rate and water loss, and improving photosynthetic efficiency and drought resistance.

Cholesterol: A friend to viruses.

Cholesterol is a key life-sustaining molecule which regulates membrane fluidity and serves as a signaling mediator. Cholesterol homeostasis is closely related to various pathological conditions including tumor, obesity, atherosclerosis, Alzheimer's disease and viral infection. Viral infection disrupts host cholesterol homeostasis, facilitating their own survival. Meanwhile, the host cells strive to reduce cholesterol accessibility to limit viral infection. This review focuses on the regulation of cholesterol metabolism and the role of cholesterol in viral infection, specifically providing an overview of cholesterol as a friend to promote viral entry, replication, assembly, release and immune evasion, which might inspire valuable thinking for pathogenesis and intervention of viral infection.

Cholesterol is a metabolically important molecule. The disruption of cholesterol homeostasis is closely related to various diseases including tumor, atherosclerosis and Alzheimer's disease. Moreover, viral infection is a highly cholesterol-dependent process. Important stages in the life cycle of viruses require the involvement of cholesterol. Viral infection breaks the cholesterol homeostasis in host cells, which is conducive to their own survival. This review aims to characterize the regulation of cholesterol metabolism and the role of cholesterol in viral infection, which would shed new light on the design of antiviral drugs.

GreenPhos, a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility.

Protein phosphorylation regulates a variety of important cellular and physiological processes in plants. In-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal phosphoproteomes. This is largely due to the need to improve protein extraction efficiency from plant cells, which have a dense cell wall, and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry analysis. To this end, we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis, rice, tomato, and Chlamydomonas reinhardtii, enabling in-depth identification with high quantitative reproducibility of about 11 000 phosphosites, the greatest depth achieved so far with single liquid chromatography-mass spectrometry (LC-MS) runs operated in a data-dependent acquisition (DDA) mode. The mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time- and cost-effectiveness. The method, named GreenPhos, combined with single-shot LC-MS, enabled in-depth quantitative identification of Arabidopsis phosphoproteins, including differentially phosphorylated spliceosomal proteins, at multiple time points during salt stress and a number of kinase substrate motifs. GreenPhos is expected to serve as a universal method for purification of plant phosphopeptides, which, if samples are further fractionated and analyzed by multiple LC-MS runs, could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

Towards performance-maximizing neural network pruning via global channel attention.

Network pruning has attracted increasing attention recently for its capability of transferring large-scale neural networks (e.g., CNNs) into resource-constrained devices. Such a transfer is typically achieved by removing redundant network parameters while retaining its generalization performance in a static or dynamic manner. Concretely, static pruning usually maintains a larger and fit-to-all (samples) compressed network by removing the same channels for all samples, which cannot maximally excavate redundancy in the given network. In contrast, dynamic pruning can adaptively remove (more) different channels for different samples and obtain state-of-the-art performance along with a higher compression ratio. However, since the system has to preserve the complete network information for sample-specific pruning, the dynamic pruning methods are usually not memory-efficient. In this paper, our interest is to explore a static alternative, dubbed GlobalPru, from a different perspective by respecting the differences among data. Specifically, a novel channel attention-based learn-to-rank framework is proposed to learn a global ranking of channels with respect to network redundancy. In this method, each sample-wise (local) channel attention is forced to reach an agreement on the global ranking among different data. Hence, all samples can empirically share the same ranking of channels and make the pruning statically in practice. Extensive experiments on ImageNet, SVHN, and CIFAR-10/100 demonstrate that the proposed GlobalPru achieves superior performance than state-of-the-art static and dynamic pruning methods by significant margins.

Sodium Carbonate-Promoted Formation of 5-Amino-1,2,4-thiadiazoles and 5-Amino-1,2,4-selenadiazoles with Elemental Sulfur and Selenium.

Sodium carbonate-promoted facile synthesis of 5-amino-1,2,4-thiadiazoles and 5-amino-1,2,4-selenadiazoles with elemental sulfur and selenium, respectively, was developed. This method was carried out with O2 in the air as the green oxidant, and it has several advantages, including low cost, low toxicity, and stable sulfur and selenium sources, good to excellent yields with water as the sole byproduct, simple operation, and a broad substrate scope. Preliminary mechanistic studies indicate that the formation of the 1,2,4-thiadiazole ring and the 1,2,4-selenadiazole ring undergoes different processes.

Electrochemically Promoted Three-Component Reaction to N-Sulfonyl Amidines.

In this study, a multicomponent reaction via the Mannich intermediate was developed using methanol, secondary amine, and sulfonamide as starting materials. This method uses methanol as a green C1 source. The substrate scope is wide, and the yield is good. The mechanistic study shows that methanol generates formaldehyde under electrochemical conditions, and sulfonyl amidine as a nucleophile reacts with Schiff base intermediates to form N-sulfonyl amidine in a single step.

Application value of plasma Neurofilament light combined with magnetic resonance imaging to comprehensively evaluate multiple sclerosis activity and status.

Objective: Compare the levels of plasma neurofilament light (NfL) in patients with multiple sclerosis (MS) at acute and remission stages and healthy individuals to explore the role of plasma NfL in monitoring the activity and severity of the disease and predicting disease prognosis. Methods: Information on healthy individuals and patients with MS who visited the outpatient and inpatient departments of Inner Mongolia Medical University Affiliated Hospital from October 2020 to August 2022 was collected. EDSS assessment and plain scan+enhanced magnetic resonance imaging (MRI). Plasma Nfl levels were measured using Simoa. Moreover, the relationship between the level of Nlf and the disease status of patients with MS was analyzed.. Results: Through the self-comparison of the plasma NfL levels of MS patients in the acute and remission stages, it was noted that the levels in the acute stage are higher than those in the remission stage (p < 0.001). Among the plasma NfL levels of healthy individuals and MS patients in the acute and remission stages, there were statistically significant differences (p < 0.001). Furthermore, the plasma NfL level did not correlate with age or course of disease (p = 0.614 and p = 0.058), whereas it correlated with EDSS score, the number of MRI T2 subtentorial and spinal cord lesions, and the number of MRI enhanced lesions (r = 0.789, p < 0.001; r = 0.846, p < 0.001; r = 0431, p = 0.005, respectively). Conclusion: Combining the level of plasma NfL with clinical and MRI estimations will be instrumental in monitoring condition changes and optimizing treatments. The level of plasma NfL is related to the activity and severity of MS, and it is expected to become a new biomarker for assessing the activity and disease status of MS.

Efficacy of ß2-adrenergic receptor agonist combined with corticosteroid in the treatment of children with cough variant asthma.

BACKGROUND: Cough variant asthma (CVA) is one of the most common respiratory diseases in children, which has a serious impact on the quality of life and daily activities of children. For severe CVA, immunomodulatory drugs are needed. AIM: To evaluate the efficacy of salmeterol combined with budesonide in the treatment of pediatric CVA. METHODS: 130 children with CVA from January 2020 to December 2022 were prospectively selected and randomly divided into an observation group (salmeterol combined with budesonide) and a control group (budesonide combined with a placebo). Compare the clinical efficacy of two groups before and after intervention. The evaluation parameters include cough frequency score, nocturnal cough arousal, and lung function indicators. Serum inflammatory markers, immune function markers and airway anatomical indicators were also measured. RESULTS: After the intervention, the total effective rate of the observation group was significantly higher than that of the control group, and the cough frequency score and the night cough wake rate of the observation group were lower than that of the control group, with a statistically significant difference. In addition, the changes of lung function indicators, serum markers and immune function markers in the observation group were better than those in the control group. CONCLUSION: The clinical efficacy of salmeterol combined with Budesonide in the treatment of CVA is better than that of Budesonide alone.

The association between blood pressure control and long-term cardiovascular outcomes in Hypertension coexistent with obstructive sleep apnea.

PURPOSE: The goal of blood pressure (BP) control will be lower when hypertensive patients have comorbidities that can affect the risk of cardiovascular diseases. But, the goal of BP control for hypertensive patients coexistent with obstructive sleep apnea (OSA) is not discussed, which is a special population at high risk of cardiovascular diseases. PATIENTS AND METHODS: Using data from a retrospective study(Urumqi Research on Sleep Apnea and Hypertension (UROSAH) study, we enrolled 3267 participants who were diagnosed with hypertension and performed polysomnography during 2011-2013 to explore the association between BP control and long-term major adverse cardiovascular and cerebrovascular event (MACCE). Outcomes of interest was the levels of BP control, MACCE, cardiac event and cerebrovascular event. Then we calculated the cumulative incidence of MACCE and performed Cox proportional hazards with stepwise models. RESULTS: 379 of 3267 patients experienced MACCE during a median follow-up of 7.0 years. After full risk adjustment, BP control of 120-139/80-89mmHg was associated with the lowest risk of cerebrovascular event (HR: 0.53, 95%CI:0.35-0.82) rather than MACCE and cardiac event in the total cohort. The association did not change much in patients with OSA. When the SBP and DBP were discussed separately, the SBP control of 120-139mmHg or < 120mmHg was associated with the decreased incidence of MACCE and cerebrovascular event. When DBP control < 80 mm Hg, the risk of cerebrovascular event showed 54% decrease [(HR:0.46, 95%CI: 0.25-0.88)] in patients with hypertension and OSA. CONCLUSION: In this retrospective study, antihypertensive-drug-induced office and home BP control at 120-139/80-89mmHg showed possible beneficial effect on incident MACCE. However, current results need to be verified in future studies.

Compact contactless conductometric, ultraviolet photometric and dual-detection cells for capillary electrophoresis via additive manufacturing.

The growing demand for tailored detectors in capillary electrophoresis (CE), addressing tasks like field deployment or dual-detection analysis, emphasizes the necessity for compact detection cells. In this work, we propose cost-effective and user-friendly additive manufacturing (3D-printing) approaches to produce such miniaturized detection cells suitable for a range of CE applications. Firstly, capacitively-coupled contactless conductivity detection (C4D) cells of different sizes are fabricated by casting low-melting-point alloy into 3D-printed molds. Various designs of Faraday shields are integrated within the cells and compared. A mini-C4D cell (9.5×7.0×7.5 mm3) is produced, with limits of detection for alkaline cations ranging from 8-12 µM in a short-capillary based CE application. Secondly, ultraviolet photometric (UV-PD) detection cells are fabricated using 3D printing. These cells feature two narrow slits with a width of 60 µm, which are positioned along the path of incident and transmission light to facilitate collimation. A deep UV-LED (235 nm or 255 nm) is employed as the light source, and black resin is determined to be the optimal material for 3D printing the UV-PD cell, owing to its superior UV light absorption capabilities. The UV-PD cell is connected to the LED and photodetector through two optical fibers, making it easy to switch the light source and detector. The effective pathlength and stray light percentage for detecting on a 75 µm id capillary are 74 µm and 0.5 %, respectively. Thirdly, a dual-detection cell that combined C4D and UV-PD at a single detection point is proposed. The performance of direct detection by C4D and indirect detection by UV-PD is compared for detecting organic acids. The strategies for developing cost-effective compact detection cells facilitate the versatile integration of multiple detection methods in CE analysis.

Lipid accumulation-mediated histone hypoacetylation drives persistent NK cell dysfunction in anti-tumor immunity.

Hyperlipidemia impairs anti-tumor immune responses and is closely associated with increased human cancer incidence and mortality. However, the underlying mechanisms are not well understood. In the present study, we show that natural killer (NK) cells isolated from high-fat-diet mice or treated with oleic acid (OA) in vitro exhibit sustainable functional defects even after removal from hyperlipidemic milieu. This is accompanied by reduced chromatin accessibility in the promoter region of NK cell effector molecules. Mechanistically, OA exposure blunts P300-mediated c-Myc acetylation and shortens its protein half-life in NK cells, which in turn reduces P300 accumulation and H3K27 acetylation and leads to persistent NK cell dysfunction. NK cells engineered with hyperacetylated c-Myc mutants surmount the suppressive effect of hyperlipidemia and display superior anti-tumor activity. Our findings reveal the persistent dysfunction of NK cells in dyslipidemia milieu and extend engineered NK cells as a promising strategy for tumor immunotherapy.

CAMSAP1 role in orchestrating structure and dynamics of manchette microtubule minus-ends impacts male fertility during spermiogenesis.

The manchette is a crucial transient structure involved in sperm development, with its composition and regulation still not fully understood. This study focused on investigating the roles of CAMSAP1 and CAMSAP2, microtubule (MT) minus-end binding proteins, in regulating manchette MTs, spermiogenesis, and male fertility. The loss of CAMSAP1, but not CAMSAP2, disrupts the well-orchestrated process of spermiogenesis, leading to abnormal manchette elongation and delayed removal, resulting in deformed sperm nuclei and tails resembling oligoasthenozoospermia symptoms. We investigated the underlying molecular mechanisms by purifying manchette assemblies and comparing them through proteomic analysis, and results showed that the absence of CAMSAP1 disrupted the proper localization of key proteins (CEP170 and KIF2A) at the manchette minus end, compromising its structural integrity and hindering MT depolymerization. These findings highlight the significance of maintaining homeostasis in manchette MT minus-ends for shaping manchette morphology during late spermiogenesis, offering insights into the molecular mechanisms underlying infertility and sperm abnormalities.

Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na+/H+ antiporter.

Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.