Nrf2, gp91phox and IL-17 are associated with severity and clinical outcomes of patients with subclinical hypothyroidism: a comparative study.

The mechanisms underlying subclinical hypothyroidism (SCH) remain unclear, making timely and accurate differentiation between hypothyroidism and SCH, as well as severity assessment, challenging. This study aimed to investigate the role of NFE2 like bZIP transcription factor 2 (Nrf2), gp91phox, and interleukin-17 (IL-17) in the pathogenesis of SCH. In this prospective comparative study, 105 SCH patients, 105 hypothyroidism patients, and 105 healthy individuals were enrolled from January 2022 to August 2023. SCH patients were categorized into mild-moderate and severe groups based on thyroid-stimulating hormone (TSH) levels. Levels of TSH, free T4 (FT4), free T3 (FT3), thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-ch), and low-density lipoprotein-cholesterol (LDL-ch) were measured. Nrf2, IL-1ß, IL-6, IL-17, and gp91phox levels were tested using ELISA. Nrf2, IL-17 and gp91phox were significantly higher in SCH and hypothyroidism patients compared to the healthy controls, with hypothyroidism patients showing the highest levels. Nrf2 levels were negatively correlated with TSH, TG-Ab and IL-17, but not gp91phox. Nrf2, IL-17 and gp91phox could be used for diagnosis of SCH and severe SCH. Only TG-Ab, IL-17 and gp91phox were independent risk factors for severe SCH. This study demonstrates a negative correlation between serum Nrf2 levels and SCH severity. TG-Ab, IL-17, and gp91phox are independent risk factors, and their associations with SCH pathology suggest their potential roles in the disease mechanism. These findings provide insights into SCH pathogenesis and highlight the need for further research to elucidate their diagnostic or prognostic significance.

First Report of Tobacco Leaf Tip Blight Caused by Alternaria gossypina in China.

Tobacco (Nicotiana tabacum L.) belongs to the family Solanaceae, an economically significant crop (Zhou et al. 2023). Twelve samples with leaf spots were collected in Keti Village, Changshun County, Zunyi City, Guizhou province, China in 2022. Twenty-five percent of the samples had dry lesions near the leaf tip which resulted leaf tip blight after development. Fungi were isolated by a previous method (Wei et al. 2022). Six Alternaria strains were obtained and preserved in the Fungal Herbarium of Yangtze University (YZU), Jingzhou, Hubei, China. Among them, one strain YZU 221477 showed distinct cultural characteristics out of five A. alternata strains, which was again determined by growing on potato dextrose agar (PDA) at 25°C for 7 days in dark to evaluate. The colonies (60 mm in diameter) were white cottony in the center surrounded by vinaceous purple. To examine the morphology, mycelia were inoculated onto potato carrot agar (PCA) at 22°C, following an 8 h light/16 h dark photoperiod (Simmons 2007). Conidia were obclavate or ovoid, normally 3-5 conidial units per chain, 20-38 × 10-16.5 µm, 3 to 5 transverse septa, beakless or a short beak (4-30 µm). The observation results were consistent with those of A. gossypina (Zhang 2003). Total genomic DNA was extracted using the CTAB method and seven gene regions including internal transcribed spacer of rDNA (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), translation elongation factor 1 alpha (TEF1), RNA polymerase second largest subunit (RPB2), Alternaria major allergen gene (Alt a 1), endopolygalacturonase (EndoPG) and an anonymous gene region (OPA10-2) were amplified with ITS5/ITS4, gpd1/gpd2, EF1-728F/EF1-986R, RPB2-5F/RPB2-7cR, Alt-for/Alt-rev, PG3/PG2b and OPA10-2L/OPA10-2R primers, respectively. All sequences were deposited in GenBank (ITS: OR710806; GAPDH: PP057862; TEF1: PP158601; RPB2: PP057863; Alt a 1: PP057865; EndoPG: PP057861; OPA10-2: PP057864). Combining with relevant sequences retrieved from the NCBI database were used for the phylogenetic analysis. Maximum Likelihood (ML) tree was constructed with RAxML v.7.2.8 employing GTRCAT model using 1000 bootstrap (BS) replicates to assess statistical support. The results indicated that the present strain grouped with A. gossypina (type strain of CBS 104.32) supported with 73% bootstrap values, also having a support of 0.83 Bayesian posterior probabilities values. Based on morphology and molecular evidence, the strain YZU 221477 is identified as Alternaria gossypina. Pathogenicity was examined to fulfill Koch's postulates. Mycelial plugs (6 mm diameter) of the present strain and A. alternata cultivated on PDA were taken from the margin and inoculated onto viable tobacco leaves (Cultivar: Yunyan 87, n=3) growing forty days, while controls were inoculated with sterile PDA. The assay was conducted three times. The plants were maintained at 25°C with humidity levels over 85% in a greenhouse. Leaves were evaluated after 7 days, necrotic spots encircled by yellow halos were on both inoculums, except controls. Pathogen re-isolation confirmed that it was the same as inoculated fungus based on morphology. A. gossypina was firstly found on cotton (Hopkins 1931), late reported to induce disease on Minneola, Nopalea, Hibiscus, Citrus, Solanum and Ageratina. To our knowledge, this is the first report of A. gossypina causing tobacco leaf tip blight in China, and it also provides a basis for controlling of tobacco leaf tip blight.

Catalyst-Substrate Helical Character Matching Determines the Enantioselectivity in the Ishihara-Type Iodoarenes Catalyzed Asymmetric Kita-Dearomative Spirolactonization.

Catalyst design has traditionally focused on rigid structural elements to prevent conformational flexibility. Ishihara's elegant design of conformationally flexible C2-symmetric iodoarenes, a new class of privileged organocatalysts, for the catalytic asymmetric dearomatization (CADA) of naphthols is a notable exception. Despite the widespread use of the Ishihara catalysts for CADAs, the reaction mechanism remains the subject of debate, and the mode of asymmetric induction has not been well established. Here, we report an in-depth computational investigation of three possible mechanisms in the literature. Our results, however, reveal that this reaction is best rationalized by a fourth mechanism called "proton-transfer-coupled-dearomatization (PTCD)", which is predicted to be strongly favored over other competing pathways. The PTCD mechanism is consistent with a control experiment and further validated by applying it to rationalize the enantioselectivities. Oxidation of the flexible I(I) catalyst to catalytic active I(III) species induces a defined C2-symmetric helical chiral environment with a delicate balance between flexibility and rigidity. A match/mismatch effect between the active catalyst and the substrate's helical shape in the dearomatization transition states was observed. The helical shape match allows the active catalyst to adapt its conformation to maximize attractive noncovalent interactions, including I(III)···O halogen bond, N-H···O hydrogen bond, and π···π stacking, to stabilize the favored transition state. A stereochemical model capable of rationalizing the effect of catalyst structural variation on the enantioselectivities is developed. The present study enriches our understanding of how flexible catalysts achieve high stereoinduction and may serve as an inspiration for the future exploration of conformational flexibility for new catalyst designs.

The effect of luteinizing hormone changes in GnRH antagonist protocol on the outcome of controlled ovarian hyperstimulation and embryo transfer.

BACKGROUD: To investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. METHODS: A total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2). RESULTS: There were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001). CONCLUSION: LH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.

Leaf Spot caused by Alternaria alternata on Macleaya cordata in China.

Macleaya cordata is a perennial herb that belongs to the Papaveraceae and is typically prescribed as a traditional antibacterial medicine in China (Kosina et al. 2010). The extract from M. cordata has been widely used in the manufacturing of natural growth promoters as an alternative to antibiotic growth promoters in the livestock industry (Liu et al. 2017), and the products are marketed in 70 countries such as Germany, China, etc (Ikezawa et al. 2009). During the summer of 2019, symptoms of leaf spot were observed on M. cordata (cv. HNXN-001) in two commercial fields (approximately 1, 300 m2 and 2, 100 m2) of Xinning county, Shaoyang City, Hunan Province, China, where approximately 2 to 3% of the plants were affected. The initial symptoms were irregular black and brown spots on the leaves. The lesions expanded and coalesced, eventually leading to leaf blight. Six symptomatic basal leaf sections from six plants from two fields were surface disinfested in 0.5% NaClO for 1 min, then 75% ethanol for 20 s, rinsed in sterile water three times, air dried, and placed onto potato dextrose agar (PDA), one dish for samples from a single leaf. Plates were incubated at 26°C in darkness. Nine strains with similar morphological characters were isolated, and one representative isolate ( BLH-YB-08) was used for morphological and molecular characterization. The colonies on PDA were grayish-green with white round margins. Conidia were typically obclavate to obpyriform, brown to dark brown, and 12.0 to 35.0 × 6.0 to 15.0 µm, and with 1 to 5 transverse septa and 0 to 2 longitudinal septa (n=50). Isolates were identified as Alternaria sp. on the basis of mycelial characteristics, color, and conidial morphology. To confirm identity of the pathogen, DNA was extracted from isolate BLH-YB-08 with the DNAsecure Plant Kit (TIANGEN, Biotech, China). The glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNA polymerase II second largest subunit (RPB2), actin (ACT), 28S nrDNA (LSU), 18S nuclear ribosomal DNA (SSU), histone 3 (HIS3), internal transcribed spacer (ITS) region of ribosomal DNA, and translation elongation factor 1-α (TEF) genes ( Berbee et al. 1999; Carbone and Kohn. 1999; Glass and Donaldson. 1995; White et al. 1990.) were amplified and sequenced. Sequences were deposited into the GenBank database. They were 100% sequence identity of GAPDH (OQ224996) with A. alternata strain AA2-8 (MH65578; 578/578bp), 100% sequence identity of RPB2 (OQ190460) with A. alternata strain SAX-WN-30-2 ( MK605877; 933/933bp), 100% sequence identity of ACT (OQ923292) with A. alternata strain FCBP0352 (OL830257; 939/939 bp), 100% sequence identity of LSU (OQ891167) with A. alternata XL14 (MG839509 ; 908/908 bp), 100% sequence identity of SSU (OQ139544) with A. alternata strain BJ19.4.1(OM736063; 1,067/1,067 bp), 100% sequence identity of HIS3 (MT454856) with A. alternata YJ-CYC-HC2 (OQ116440 ; 442/442 bp), 100% sequence identity of ITS (MT212225) with A. alternata CS-1-3 (OQ947366; 543/543bp), and 100% sequence identity of TEF (OQ190461) with A. alternata strain YZU 221185 (OQ512730; 252/252 bp). To test pathogenicity, the isolate BLH-YB-08 was cultured on PDA for 7 days to prepare conidial suspensions and the spore concentration adjusted to a final concentration of 1×106 spores/ml. The leaves of five potted 45-day-old M. cordata (cv. HNXN-001) plants were sprayed with conidial suspensions, and five control potted plants were wiped with 75% alcohol and washed five times with sterile distilled water. They were then sprayed with sterile distilled water. Plants were placed in a greenhouse at 25 to 30°C with 90% relative humidity. Pathogenicity tests were conducted twice. Fifteen days after inoculation, lesions were found on inoculated leaves, and the symptoms were the same as those in the field, whereas the controls were healthy. A fungus was consistently isolated from the inoculated leaves and identified as A. alternata by DNA sequencing of the GAPDH, ITS, and HIS3 genes, fulfilling Koch's postulates. To our knowledge, this is the first report of leaf spot on M. cordata caused by A. alternata in China. Understanding its etiology may help to control this fungal pathogen, thus reducing economic losses. Funding: Hunan Provincial Natural Science Foundation General Project (2023JJ30341) Hunan Provincial Natural Science Foundation Youth Fund (2023JJ40367) Seed Industry Innovation Project of Hunan Provincial Science and Technology Department Special project for the construction of Chinese herbal medicine industry technology system in Hunan Province "Xiangjiuwei" Industrial Cluster Project of the Ministry of Agriculture and Rural Affairs.

NIR Responsive Injectable Nanocomposite Thermogel System Against Osteosarcoma Recurrence.

Compared to traditional postoperative radiation and chemotherapy, immune checkpoint blockade (ICB) therapy demonstrates superiority by provoking own immune system to cure cancer completely even for some terminally ill patients. However, systemic administration of ICB is liable to cause severe immunity inflammation or immune storm. Here, an injectable, near infrared (NIR) responsive, multifunctional nanocomposite thermogel as a local ICB delivery system for cancer postsurgical therapy is proposed. By copolymerization of thermosensitive and zwitterionic monomer, the injectable thermogel with adjustable sol-gel transition temperature is obtained. Afterward, combined with functional mesoporous nanoparticles, the platform can absorb NIR light and transfer it into heat. The generated heat will promote retro Diels-Alder (D-A) reaction to degrade coating layer on nanoparticle, achieving NIR controlled ICB release. Furthermore, the local ICB delivery system is applied on an osteosarcoma postsurgical recurrence model and results indicate the platform with favorable biocompatibility can avoid early leakage of cargos and greatly increase drug content at tumor site. Besides, long-term controlled ICB release of the system effectively improves the amount of active T cells, resulting in excellent antitumor recurrence effect. Overall, this work suggests the local injectable nanocomposite thermogel is expected to be a promising tool for cancer postoperative therapy.

Analysis of Thoracic Aorta Injury in 27 Road Traffic Accident Deaths.

OBJECTIVES: To analyze the characteristics of thoracic aorta injury in road traffic accidents, to provide data reference for forensic identification. METHODS: The data of 27 traffic accident death cases with thoracic aorta injury were analyzed according to relevant parameters including sex, age, mode of transportation, and thoracic aorta injury. RESULTS: Aortic injury in traffic accidents was significantly more in males than females, and 74.1% cases were in the age range of 31-70 years. The most common mode of transportation was the motorcycle, followed by electric bike, most of which crashed with trucks. Most cases were accompanied by rib fractures and lung injuries. Thoracic aorta injury was the most common in ascending aorta, followed by aortic arch and thoracic aorta. Ascending aorta injury was most likely to occur in the range of 0-<1.6 cm from the aortic valve, while it was rare over 2.6 cm. Taking the aortic valve as the reference, the most common locations of injury were the anterior semilunar valve, followed by the right posterior semilunar valve and the left posterior semilunar valve. Thoracic aortic rupture occurred in 63.0% cases, and intima and media lacerations only occurred in 37.0% cases. A few deceased had aortic diseases. CONCLUSIONS: The proximal part of the ascending aorta is prone to be injured because of the large external force of traffic accidents. The medical examiner should carefully examine the aortic injury in traffic accident deaths, and evaluate the relationship between the injury and the disease according to the condition and degree of aortic injury.

Hematologic and spirometric characteristics of Tajik and Kyrgyz highlanders in the Pamir Mountains.

OBJECTIVES: In this study, we measured the hematologic and spirometric parameters of native Tajik and Kyrgyz highlanders in the Pamir Mountains to investigate adaptations to high altitude stressors. METHODS: Hematological parameters including arterial oxygen saturation (SaO2 ), red blood cell (RBC) counts, and hemoglobin (Hb) concentration were measured on Sarikoli Tajik (n = 80; 3100 m), Wakhi Tajik (n = 48; 3500 m), and Kyrgyz (n = 64; 3250 m) in comparison to lowland Uyghurs (n = 50; 1300 m). Spirometric parameters including forced vital capacity (FVC), the first second of forced expiration (FEV1), and forced expiratory flow between 25% and 75% (FEF25-75) were measured. We also reported mountain sickness symptoms in these highlanders and conducted a multivariate regression analysis to analyze the association between these symptoms and the measured parameters. RESULTS: SaO2 of Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (91%-93.5%) are significantly lower than lowland Uyghurs, yet are comparable to other native highlanders at a similar altitude. RBC counts and Hb concentrations of all three highland populations are significantly increased compared to Uyghurs. FVC is lower in Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (male: 3.48-3.86 L, female: 2.47-2.78 L) compared to Uyghurs. Combined with normal FEV1, elevated FEV1/FVC ratio, and FEF25-75, the spirometric patterns of these highlanders indicate restrictive lung disease. A high prevalence of mountain sickness symptoms such as headache and nausea was found in all three highland populations, and are attributed to low FVC and aging by regression analysis. CONCLUSION: Tajik and Kyrgyz highlanders showed adaptation in SaO2 , RBC, and Hb level, but poor performance in spirometry, which causes mountain sickness.

First Report of Leaf spot Caused by Xylaria arbuscula on Flue-cured Tobacco in China.

Flue-cured tobacco (Nicotiana tabacum L.) is a leafy, annual, solanaceous plant grown commercially for its leaves in China. Around 70% of tobacco production in China occurs in southwest China. In summer of 2019, leaf spot symptoms were observed on ten to twenty percent of tobacco plants in a 2 ha commercial field of Bijie (27.32° N, 105.29° E), Guizhou province, China. The leaf spots were white with dark-brown in edges, irregularly round and oval, and diseased tissue dropped out leaving the leaves ragged in appearance (Fig. 1A, 1B). One diseased leaf from each of five plants was sampled. From five leaves, a total of 15 small (5 mm × 5 mm) pieces of leaf tissue were cut from the edge of the lesions after surface sterilization and placed on potato dextrose agar (PDA) medium. Five fungal colonies that were similar in appearance were isolated and one was purified, BEZ22, was selected arbitrarily for identification. Mycelia of the pathogen was initally white and dense, and then black carbonized mycelia appeared from the center of the colony 7 days' after incubation. Mycelia was white, sparse and radiated when incubated on OA (oatmeal agar) (Fig. 1E, 1F, 1G, 1H). Genomic DNA of the isolate was extracted. The internal transcribed spacers (ITS) with primers ITS1/ITS4 (White et al. 1990), actin (ACT) gene with primers ACT-512F/ACT-738R (Hsieh et al. 2005), beta-tubulin (TUB2) with primers T1/T22 (O'Donnell & Cigelnik 1997) and RNA polymerase II second largest subunit gene (RPB2) with primers fRPB2-5F/ fRPB2-7cR (Liu et al. 1999) were amplified and sequenced, respectively. The generated sequences were deposited in GenBank with accession numbers MT804353 (ITS), MT809582 (ACT), MT799790 (TUB2) and MT799789 (RPB2). Using BLASTN searches, the sequences of each gene above were aligned with the voucher specimum, Xylaria arbuscula 89041211. The number of nucleotides that were similar for ITS (GU300090) was 550/551 (99%); for ACT (GQ421286), 266/266 bp (100%); for TUB2 (GQ478226), 1501/1501 bp (100%); and for RPB2 (GQ844805), 1135/1135 bp (100%), respectively (Fig. 2). A phylogenetic tree was constructed based on these four sequences with a final alignment of 3456 characters (ITS 551, ACT 266, TUB2 1501 and RPB2 1138). Thus, based on morphological and phylogenetic analyses, the isolate BEZ22 was identified as Xylaria arbuscula. To verify pathogenicity, six tobacco plants at seedling stage (5-6 leaves) without visible disease were inoculated using mycelial plugs (5 mm in diameter). Leaves inoculated with PDA only plugs served as controls. After inoculation, all tobacco plants were maintained in a greenhouse with 85% relative humidity at 25 oC under a 12/12 h light/dark cycle. Five days after inoculation, typical early symptoms were observed on the inoculated leaves, and not on the control leaves. Koch's postulates were fulfilled by re-isolation of the pathogen from diseased leaves. Xylaria arbuscula has also been reported as a pathogen of Macadamia in Hawaii (Wenhsiung et al. 2009) and sugarcane in Indonesia (Maryono et al. 2020). However, to our best knowledge, this is the first report of X. arbuscula causing leaf spot on tobacco in China. This leaf spot has the potential to cause serious damage to tobacco in this region that could result in reduced production, consequently disease management of this pathogen should be considered.

Acoustic inversion method for parameters of sediments based on adaptive predatory genetic algorithm.

Acoustic inversion for the physical parameters of seafloor sediments is an important and difficult aspect of sediment acoustic research. Submarine surface sediments are typical porous media, which involve many parameters. Thus, the optimization of high-dimensional inversion represents one of the difficulties. An acoustic inversion method to obtain the physical parameters of seafloor sediments is constructed based on the adaptive predatory genetic algorithm and effective density fluid model derived from Biot theory. The method introduces the adaptive process and predatory strategy into the genetic algorithm and uses the norm of the relative difference between the predicted wave number and the measured wave number as the objective function. The method is confirmed to be stable and efficient by simulated data and is also applied to invert porosity, tortuosity, and permeability of the sediments in Hangzhou Bay of China using acoustic data measured by an in situ acoustic measurement system.

Study on Determination of Molybdenum in Molybdenum Concentrate by Atomic Absorption Spectrometry Indirectly.

For the determination of molybdenum in molybdenum concentrate，lead molybdate gravimetric method was considered as standard method. In order to ensure the lead ions to be washed thoroughly from the entrained precipitate, lead molybdate precipitate was washed, filtered repeatedly, then ashed and burned. This method cannot satisfy the rapid measurement demand of mineral processing and metallurgy scientific research due to its time consuming. In the present work, molybdenum was determined by atomic absorption spectrometry indirectly and a rapid analysis method for molybdenum in molybdenum concentrate was proposed. The sample was dissolved by nitric acid, potassium chlorate and sulfuric acid, pH was adjusted by acetic acid and ammonium acetate buffer solution to pH 5～7, then a certain amount and excess of lead standard was added. Based on lead molybdate was considered as undissolved electrolyte on room temperature, the solubility of lead molybdate was 1.16×10-5g, far less than 0.01 g, was considered as the undissolved electrolyte, the electrolyte insoluble at a certain temperature can complete precipitation, usually compared with the solubility production product Qc and the relative size of constant Ksp, when Qc>Ksp, solution was supersaturated, precipitation was precipitate completely, the content of molybdenum in molybdenum concentrate was 40%~60%, the amount of lead was 0.125 0~0.150 0 g, took the minimum calculated solution lead molybdate ion product, Qc＝[Pb2+][MoO2-4]=2.51×10-5，Ksp＝1.0×10-13，QcKsp，Therefore lead molybdate precipitate can be precipitated completely, after dry filtered, the excess of lead ions were determined by atomic absorption spectrometry, the content of molybdenum was calculated by subtraction method. In this paper, the amount of acetic acid-ammonium acetate buffer solution, the amount of lead standard, time of lead molybdate precipitation, heating time and maximum amount of coexisting ions such as W6+, Sn4+, Cu2+, etc were investigated. Compared with lead molybdate gravimetric method, repeatedly washing, ashing and burning with lead molybdate were eliminated by proposed method, which was simple, easy to master and was able to cut the analysis time in half. The control experiments were conducted by lead molybdate gravimetric method and proposed method. After the results were implemented by mathematical statistics, it can be concluded that it had good accuracy and precision for the proposed method, which can be applied to rapid analysis of molybdenum in molybdenum concentrate for mineral processing and metallurgy.

Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. MATERIAL AND METHODS: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. RESULTS: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = -3.160, p = 0.042). CONCLUSIONS: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.

Mussel shell-derived pro-regenerative scaffold with conductive porous multi-scale-patterned microenvironment for spinal cord injury repair.

It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinkedin situwithin the mussel shells.In vitroexperiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.

[Application of anterior-inferior approach through retrohepatic tunnel for dissecting short hepatic veins in laparoscopic right hemihepatectomy].

OBJECTIVE: To explore the safety and feasibility of laparoscopic right hemihepatectomy via an anterior-inferior approach through retrohepatic tunnel in the dissection of short hepatic veins (SHVs). METHODS: After partial freeing of right liver, anterior peritoneum of inferior cava vena (ICV) was opened. Retrohepatic space was dissected via an anterior-inferior approach to establish the posterior tunnel partially. Then the first branch of right side SHVs could be freed and ligated after its exposure through the right part of retrohepatic tunnel. The above procedure was repeated until the right side SHVs or the third hepatic portal became partially or completely blocked. If right side SHVs were completely freed and ligament of right liver fully isolated, right hepatic vein could be exposed and ligated and selective blockage of the second hepatic portal blood flow accomplished. This technique was applied in 7 cases of laparoscopic right hemihepatectomy through curettage transaction and aspiration with laparoscopic Peng's multifunctional operative dissector (LPMOD). RESULTS: Six patients were treated successfully. In one case of right hepatic hemangioma, small margin auxiliary hematischesis was attempted because of troublesome hemostasis of middle hepatic vein branch. All of them underwent partial dissection of right side of SHVs. Two cases had complete dissection in which right hepatic vein was freed and ligated, the second hepatic porta blood flow controlled and right hemihepatectomy anatomically achieved. Operative duration was 300-540 min [mean, 399.1 ± 74.7]. The time of dissecting hepatic porta was 30-75 min [mean, 50.7 ± 16.2]. The time of dissecting SHVs was 35-95 min [mean, 57.1 ± 22.1]. The time of liver transection was 60-160 min [mean, 115.9 ± 32.3]. Operative blood loss had a volume at 600-3000 ml [mean, 1485.7 ± 809.2]. The postoperative hospital stay was 10-18 days [mean, 12.4 ± 2.6]. The postoperative time for ambulation, diet and flatus was 2-4, 1-4 and 2-4 days respectively. No severe postoperative complications occurred. CONCLUSION: During laparoscopic right hemihepatectomy, dissecting SHVs is both safe and feasible through a retrohepatic tunnel via an anterior-inferior approach.

[Application of bio-mesh-reinforced pancreatico-gastrostomy after pancreaticoduodenectomy].

OBJECTIVE: To evaluate the clinical efficacy of bio-mesh-reinforced pancreaticogastrostomy. METHODS: A total of 23 patients undergoing bio-mesh-reinforced pancreaticogastrostomy from May 2011 to January 2013 were retrospectively analyzed. Their demographic data, operative parameters and post-operative outcomes were recorded. The severity of pancreatic leak was determined according to the criteria of International Study Group on Pancreatic Fistula (ISGPF). RESULTS: The mean anastomotic time was 24 (20-35) minutes. Intra-operative leak tests showed all pancreatic anastomoses were watertight. Six patients (26.1%) had pancreatic leakage of grade A. One patient (4.3%) had pancreatic leakage of grade B. No patient developed postoperative pancreatic leakage of class C. One case of abdominal infection was reported. No severe complications such as hemorrhage, bile leakage or gastrojejunostomy leakage were observed. All patients recovered well within Month 1 post-discharge. CONCLUSION: This novel technique may be a simple and feasible strategy for all types of pancreatic remnants.

Natural polysaccharides exert anti-tumor effects as dendritic cell immune enhancers.

With the development of immunotherapy, the process of tumor treatment is also moving forward. Polysaccharides are biological response modifiers widely found in plants, animals, fungi, and algae and are mainly composed of monosaccharides covalently linked by glycosidic bonds. For a long time, polysaccharides have been widely used clinically to enhance the body's immunity. However, their mechanisms of action in tumor immunotherapy have not been thoroughly explored. Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells (APCs) that play a crucial role in the regulation and maintenance of the immune response. There is growing evidence that polysaccharides can enhance the essential functions of DCs to intervene the immune response. This paper describes the research progress on the anti-tumor immune effects of natural polysaccharides on DCs. These studies show that polysaccharides can act on pattern recognition receptors (PRRs) on the surface of DCs and activate phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), Dectin-1/Syk, and other signalling pathways, thereby promoting the main functions of DCs such as maturation, metabolism, antigen uptake and presentation, and activation of T cells, and then play an anti-tumor role. In addition, the application of polysaccharides as adjuvants for DC vaccines, in combination with adoptive immunotherapy and immune checkpoint inhibitors (ICIs), as well as their co-assembly with nanoparticles (NPs) into nano drug delivery systems is also introduced. These results reveal the biological effects of polysaccharides, provide a new perspective for the anti-tumor immunopharmacological research of natural polysaccharides, and provide helpful information for guiding polysaccharides as complementary medicines in cancer immunotherapy.

Ammonium Persulfate-Loaded Carboxylic Gelatin-Methacrylate Nanoparticles Promote Cardiac Repair by Activating Epicardial Epithelial-Mesenchymal Transition via Autophagy and the mTOR Pathway.

Restoring damaged myocardial tissue with therapeutic exogenous cells still has some limitations, such as immunological rejection, immature cardiac properties, risk of tumorigenicity, and a low cell survival rate in the ischemic myocardium microenvironment. Activating the endogenous stem cells with functional biomaterials might overcome these limitations. Research has highlighted the multiple differentiation potential of epicardial cells via epithelial-mesenchymal transition (EMT) in both heart development and cardiac regeneration. In our previous research, a carboxylic gelatin-methacrylate (carbox-GelMA) nanoparticle (NP) was fabricated to carry ammonium persulfate (APS), and APS-loaded carbox-GelMA NPs (NPs/APS) could drive the EMT of MCF-7 cells in vitro and promote cancer cell migration and invasion in vivo. The present study explored the roles of functional NPs/APS in the EMT of Wilms' tumor 1-positive (WT1+) epicardial cells and in the repair of myocardial infarction (MI). The WT1+ epicardial cells transformed into endothelial-like cells after being treated with NPs/APS in vitro, and the cardiac functions were improved significantly after injecting NPs/APS into the infarcted hearts in vivo. Furthermore, simultaneous activation of both autophagy and the mTOR pathway was confirmed during the NPs/APS-induced EMT process in WT1+ epicardial cells. Together, this study highlights the function of NPs/APS in the repair of MI.

Laparoscopic vs open radical resection in management of gallbladder carcinoma: A systematic review and meta-analysis.

BACKGROUND: Radical resection offers the only hope for the long-term survival of patients with gallbladder carcinoma (GBC) above the T1b stage. However, whether it should be performed under laparoscopy for GBC is still controversial. AIM: To compare laparoscopic radical resection (LRR) with traditional open radical resection (ORR) in managing GBC. METHODS: A comprehensive search of online databases, including Medline (PubMed), Cochrane Library, and Web of Science, was conducted to identify comparative studies involving LRR and ORR in GBCs till March 2023. A meta-analysis was subsequently performed. RESULTS: A total of 18 retrospective studies were identified. In the long-term prognosis, the LRR group was comparable with the ORR group in terms of overall survival and tumor-free survival (TFS). LRR showed superiority in terms of TFS in the T2/tumor-node-metastasis (TNM) Ⅱ stage subgroup vs the ORR group (P = 0.04). In the short-term prognosis, the LRR group had superiority over the ORR group in the postoperative length of stay (POLS) (P < 0.001). The sensitivity analysis showed that all pooled results were robust. CONCLUSION: The meta-analysis results show that LRR is not inferior to ORR in all measured outcomes and is even superior in the TFS of patients with stage T2/TNM Ⅱ disease and POLS. Surgeons with sufficient laparoscopic experience can perform LRR as an alternative surgical strategy to ORR.

Characteristics of Epicoccum latusicollum as revealed by genomic and metabolic phenomic analysis, the causal agent of tobacco Epicoccus leaf spot.

Epicoccum latusicollum is a fungus that causes a severe foliar disease on flue-cured tobacco in southwest China, resulting in significant losses in tobacco yield and quality. To better understand the organism, researchers investigated its optimal growth conditions and metabolic versatility using a combination of traditional methods and the Biolog Phenotype MicroArray technique. The study found that E. latusicollum exhibited impressive metabolic versatility, being able to metabolize a majority of carbon, nitrogen, sulfur, and phosphorus sources tested, as well as adapt to different environmental conditions, including broad pH ranges and various osmolytes. The optimal medium for mycelial growth was alkyl ester agar medium, while oatmeal agar medium was optimal for sporulation, and the optimum temperature for mycelial growth was 25°C. The lethal temperature was 40°C. The study also identified arbutin and amygdalin as optimal carbon sources and Ala-Asp and Ala-Glu as optimal nitrogen sources for E. latusicollum. Furthermore, the genome of E. latusicollum strain T41 was sequenced using Illumina HiSeq and Pacific Biosciences technologies, with 10,821 genes predicted using Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. Analysis of the metabolic functions of phyllosphere microorganisms on diseased tobacco leaves affected by E. latusicollum using the Biolog Eco microplate revealed an inability to efficiently metabolize a total of 29 carbon sources, with only tween 40 showing some metabolizing ability. The study provides new insights into the structure and function of phyllosphere microbiota and highlights important challenges for future research, as well as a theoretical basis for the integrated control and breeding for disease resistance of tobacco Epicoccus leaf spot. This information can be useful in developing new strategies for disease control and management, as well as enhancing crop productivity and quality.

Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical-Electrical Anisotropic Microenvironment for Heart Repair.

The biomimetic construction of a microstructural-mechanical-electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction (MI). Inspired by the 3D anisotropic characteristic of the natural fish swim bladder (FSB), a novel flexible, anisotropic, and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural, conductive, and mechanical features of the native cardiac extracellular matrix. The results revealed that the originally stiff, homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel, enabling its potential as a functional engineered cardiac patch (ECP). In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity, maturation, elongation, and orientation of cardiomyocytes (CMs), and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis, thereby promoting cell retention, myogenesis, and vascularization, as well as improving electrical integration. Our findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.