Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

Ionic and electronic polarization effects in horizontal hybrid perovskite device structures close to equilibrium.

The electrical response of hybrid perovskite devices carries a significant signature from mobile ionic defects, pointing to both opportunities and threats when it comes to functionality, performance and stability of these devices. Despite its importance, the interpretation of polarization effects due to the mixed ionic-electronic conducting nature of these materials and the quantification of their ionic conductivities still poses conceptual and practical challenges, even for the equilibrium situation. In this study, we address these questions and investigate the electrical response of horizontal devices based on methylammonium lead iodide (MAPI) close to equilibrium conditions. We discuss the interpretation of DC polarization and impedance spectroscopy measurements in the dark, based on calculated and fitted impedance spectra obtained using equivalent circuit models that account for the mixed conductivity of the perovskite and for the effect of device geometry. Our results show that, for horizontal structures with a gap width between the metal electrodes in the order of tens of microns, the polarization behavior of MAPI is well described by the charging of the mixed conductor/metal interface, suggesting a Debye length in the perovskite close to 1 nm. We highlight a signature in the impedance response at intermediate frequencies, which we assign to ionic diffusion in the plane parallel to the MAPI/contact interface. By comparing the experimental impedance results with calculated spectra for different circuit models, we discuss the potential role of multiple mobile ionic species and rule out a significant contribution from iodine exchange with the gas phase in the electrical response of MAPI close to equilibrium. This study helps to clarify the measurement and interpretation of mixed conductivity and polarization effects in hybrid perovskites with immediate relevance to the characterization and development of transistors, memristors and solar cells based on this class of materials as well as other mixed conductors.

High-performance dual-tunable terahertz absorber based on strontium titanate and bulk Dirac semimetal for temperature sensing and switching function.

In this study, a perfect metamaterial absorber based on strontium titanate and bulk Dirac semimetals is proposed. When the temperature of strontium titanate was 300K, the dual-band absorptions were 99.74% and 99.99% at 1.227 and 1.552 THz, respectively. The sensitivities based on a transverse magnetic (TM) wave were 0.95 and 1.22 GHz/K; the sensitivity based on a transverse electric (TE) wave was 0.76 GHz/K. The TE and TM waves were modulated by inserting a bulk Dirac semimetal between the concave and convex devices. The modulation depth of the TE wave was 97.9% at 1.1 THz; the extinction ratio was 16.9 dB. The modulation depth of the TE wave at 1.435 THz was 95.9%; the extinction ratio was 13.89 dB. The TM wave modulation depth at 1.552 THz was 95.9%; the extinction ratio was 13.98 dB. Irrespective of a TE or TM wave, the terahertz absorber has good switching and temperature-sensing performance based on strontium titanate and bulk Dirac semimetals as well as broad application prospects in temperature sensing and switching devices.

Identification and Mutation Analysis of Nonconserved Residues on the TIM-Barrel Surface of GH5_5 Cellulases for Catalytic Efficiency and Stability Improvement.

Exploring the potential functions of nonconserved residues on the outer side of α-helices and systematically optimizing them are pivotal for their application in protein engineering. Based on the evolutionary structural conservation analysis of GH5_5 cellulases, a practical molecular improvement strategy was developed. Highly variable sites on the outer side of the α-helices of the GH5_5 cellulase from Aspergillus niger (AnCel5A) were screened, and 14 out of the 34 highly variable sites were confirmed to exert a positive effect on the activity. After the modular combination of the positive mutations, the catalytic efficiency of the mutants was further improved. By using CMC-Na as the substrate, the catalytic efficiency and specific activity of variant AnCel5A_N193A/T300P/D307P were approximately 2.0-fold that of AnCel5A (227 ± 21 versus 451 ± 43 ml/s/mg and 1,726 ± 19 versus 3,472 ± 42 U/mg, respectively). The half-life (t1/2) of variant AnCel5A_N193A/T300P/D307P at 75°C was 2.36 times that of AnCel5A. The role of these sites was successfully validated in other GH5_5 cellulases. Computational analyses revealed that the flexibility of the loop 6-loop 7-loop 8 region was responsible for the increased catalytic performance. This work not only illustrated the important role of rapidly evolving positions on the outer side of the α-helices of GH5_5 cellulases but also revealed new insights into engineering the proteins that nature left as clues for us to find. IMPORTANCE A comprehensive understanding of the residues on the α-helices of the GH5_5 cellulases is important for catalytic efficiency and stability improvement. The main objective of this study was to use the evolutionary conservation and plasticity of the TIM-barrel fold to probe the relationship between nonconserved residues on the outer side of the α-helices and the catalytic efficiency of GH5_5 cellulases by conducting structure-guided protein engineering. By using a four-step nonconserved residue screening strategy, the functional role of nonconserved residues on the outer side of the α-helices was effectively identified, and a variant with superior performance and capability was constructed. Hence, this study proved the effectiveness of this strategy in engineering GH5_5 cellulases and provided a potential competitor for industrial applications. Furthermore, this study sheds new light on engineering TIM-barrel proteins.

Photo-Effect on Ion Transport in Mixed Cation and Halide Perovskites and Implications for Photo-Demixing*.

Lead halide perovskites are considered to be most promising photovoltaic materials. Highest efficiency and improved stability of perovskite solar cells have been achieved by using cation and anion mixtures. Experimental information on electronic and ionic charge carriers is key to evaluate device performance, as well as processes of photo-decomposition and photo-demixing which are observed in these materials. Here, we measure ionic and electronic transport properties and investigate various cation and anion substitutions with a special eye on their photo-ionic effect, following our previous study on CH3 NH3 PbI3 , where we found that light enhances not only electronic but also ionic conductivities. We find that this phenomenon is very sensitive to the nature of the halide, while the cationic substitutions are less relevant. Based on the observation that the ionic conductivity enhancement found for iodide perovskites is significantly weakened by bromide substitution, we provide a chemical rationale for the photo-demixing in mixed halide compositions.

Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.

Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)-induced depression through regulation of the TGF-ß1 signal transduction pathway. Verification of the targeting relationship between miR-192-5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual-luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR-192-5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS-induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF-ß1 signaling pathway, and decreased expression of miR-192-5p, synaptophysin, brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, and calmodulin-dependent protein kinase II were noted. Up-regulated miR-192-5p targeting Fbln2 acts to alleviate CUMS-induced depression by inhibiting the TGF-ß1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up-regulated levels of miR-192-5p expression act to suppress activation of the TGF-ß1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression.-Tang, C.-Z., Yang, J.-T., Liu, Q.-H., Wang, Y.-R., Wang, W.-S. Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.

Identification and characterization of a novel L-type lectin (MjLTL2) from kuruma shrimp (Marsupenaeus japonicus).

L-type lectins (LTLs) belong to the lectin family and are characterized by a conserved structural motif in their carbohydrate recognition domain. LTLs are homologous to leguminous lectins. In this study, we identified and functionally characterized an LTL from kuruma shrimp Marsupenaeus japonicus. We designated this LTL as MjLTL2. MjLTL2 contains a signal peptide, a Lectin_leg domain, a coiled coil, and transmembrane domain. MjLTL2 is distributed in hemocytes, heart, hepatopancreas, gill, stomach, and intestine; higher expression levels are seen in hemocytes and the hepatopancreas than in other tissues. MjLTL2 was upregulated following challenge of shrimp with Vibrio anguillarum and white spot syndrome virus (WSSV). MjLTL2 can agglutinate several bacteria without Ca2+. In addition, MjLTL2 could bind to several Gram-positive and -negative bacteria by binding to their lipopolysaccharide and peptidoglycan. However, MjLTL2 could not enhance the clearance of V. anguillarum in vivo. In the presence of WSSV infection, MjLTL2 knockdown by RNA interference resulted in a 7-day lower cumulative mortality of M. japonicus. Moreover, less VP19, VP24, VP26, and VP28 mRNAs were extracted from the hemocytes of MjLTL2 knockdown shrimp than from the control. These results suggest that MjLTL2 is involved in immune responses in shrimp.

Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery.

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

Silence of ryanodine receptor gene decreases susceptibility to chlorantraniliprole in the oriental armyworm, Mythimna separata Walker.

The ryanodine receptors of insects are the main target sites of diamide insecticides, which show highly selective insecticidal activity relative to toxicity in mammals and provide a novel option for managing lepidopteran pests. The oriental armyworm, Mythimna separata (Walker), is a destructive pest of agricultural crops, and great efforts have been undertaken to control this pest including repeated insecticide applications. In this study, full-length cDNA of a ryanodine receptor gene from M. separata (MsRyR) was cloned and characterized. The cDNA of MsRyR had a 15,372 bp open reading frame and encoded 5124 amino acids (GenBank ID: MG712298). MsRyR shares 78-97% identity with RyR isoforms of other insects, and <50% identities with Homo sapiens RyRs 1-3. Temporal and spatial expression analysis detected MsRyR at all developmental stages and in all tissues. The highest relative levels of MsRyR were detected in the second instar and head. Exposure to chlorantraniliprole after 24 h significantly increased the expression levels of whole body MsRyR mRNA. In addition, dietary ingestion of dsMsRyR significantly reduced the mRNA level of MsRyR and greatly decreased chlorantraniliprole-induced mortality. Our results revealed that the MsRyR could be the molecular target of chlorantraniliprole, and provided the basis for further understanding the resistance mechanism of chlorantraniliprole.

[Lithagogue effects of Pyrrosia lingua from Guizhou province on experimental renal calculus in rats].

To screen the active fractions with lithagogue effects of Pyrrosia lingua from Guizhou province and preliminarily investigate its mechanism. The rats were fed with 1% ethylene glycol and 2% ammonium chloride to establish the nephrolithiasis models, which were used to evaluate thelithagogue effects of different polar fractions of P. lingua from Guizhou province. The level of urinary calcium and oxalic acid in urine, renal calcium, oxalic acid, superoxide dismutase (SOD), catalase(CAT) and malondialdehyde (MDA) in renal tissues,as well as crystalline deposit and lithogenesis in renal tissues and the levels of creatinine(Cr) and blood urea nitrogen (BUN) in the serum were detected. The effective compounds were inferred from the analysis of active fractions extract based on LC-MS technology. Petroleum ether fraction and dichloromethane fraction of P. lingua from Guizhou province can reduce renal oxalic acid and renal calcium concentration, increase urinary oxalic acid and urine calcium, with significant inhibitory effect on the formation of renal calculus in rats, significantly increase SOD and CAT activities in renal tissues, and significantly reduce MDA levels. LC-MS analysis showed that the caffeine, citric acid and tartaric acid among the compounds from petroleum ether fraction and dichloromethane fraction had lithagogue effects. Both the petroleum ether fraction and dichloromethane fraction of P. lingua from Guizhou province showed good effect on prevention and treatment of calculus in middle dose groups, and the mechanism may be associated with antioxidation, reducing calcium oxalate crystal deposition, and promoting calcium oxalatecrystal release, in addition, caffeine, citric acid and tartaric acid had lithagogue effects.

[Application of Multi-Test II prick device in the skin prick test for allergens in children].

OBJECTIVE: To study the applicability of Multi-Test II prick device in the skin prick test (SPT) for allergens in children. METHODS: A total of 87 children with allergic diseases who attended the hospital between March and September, 2017 were enrolled as subjects. The SPT for six inhaled allergens and serum specific IgE (sIgE) measurement were performed for all children. SPT was performed with a single-headed device on the left forearm and Multi-Test II prick device on the right forearm. ELISA was used to measure the serum level of sIgE. Visual Analog Scale (VAS) was used to assess the degree of pain during SPT. The three methods were compared in terms of the detection rates of six allergens, and the sensitivity and specificity of Multi-Test II prick device were analyzed. RESULTS: There were no significant differences in the detection rates of six allergens among the Multi-Test II method, the single-headed method, and ELISA (P>0.05). Compared with the single-headed method, the Multi-Test II method had a sensitivity of 72.7% and a specificity of 78.2%. Compared with ELISA, the Multi-Test II method had a sensitivity of 73.4% and a specificity of 77.5%. The Multi-Test II method had a significantly lower degree of pain than the single-headed method (P<0.05). CONCLUSIONS: The Multi-Test II method has high sensitivity and specificity and is easily accepted by children, but the test results should be combined with children's medical history and serum level of sIgE when necessary.

[Distribution characteristics of serum specific IgE for inhaled allergens in children with different airway allergic diseases].

OBJECTIVE: To investigate the distribution characteristics of serum specific IgE (sIgE) for inhaled allergens in children with different airway allergic diseases. METHODS: Fluorescent enzyme-linked immunosorbent assay on the UniCAP250 system was performed to measure serum sIgE for 9 common inhaled allergens in 256 children aged 3-14 years with different airway allergic diseases. According to the clinical diagnosis, these children were divided into rhinitis group (37 children with allergic rhinitis), asthma group (82 children with bronchial asthma), and rhinitis-asthma group (137 children with allergic rhinitis complicated by bronchial asthma). The three groups were compared in terms of the detection rates of 9 inhaled allergens, sensitization level, and number of allergens. RESULTS: The detection rate of serum sIgE for inhaled allergens was 57.3% (47/82) in the asthma group, 86.5% (32/37) in the rhinitis group, and 82.5% (113/137) in the rhinitis-asthma group (P<0.05). The most common allergen in the asthma, rhinitis, and the rhinitis-asthma groups was mould fungi (32.9%, 54.1%, and 48.9% respectively), followed by dust mites (30.5%, 45.9%, and 46.0% respectively), pollen (26.8%, 35.1%, and 32.8% respectively), pets (12.2%, 27.0%, and 18.2% respectively), and cockroach (9.8%, 5.4%, and 5.8% respectively). The rhinitis group and the rhinitis-asthma group had a significantly higher detection rate of mould fungi (mx2) than the asthma group (P<0.0166). There were no significant differences in the sensitization level of 9 allergens and number of allergens between the three groups. CONCLUSIONS: In children with either bronchial asthma, allergic rhinitis, or bronchial asthma complicated by allergic rhinitis, the three most common inhaled allergens are mould fungi, dust mites, and pollens. Compared with bronchial asthma, allergic rhinitis may be more closely associated with sensitization by mould fungi. The three common airway allergic diseases have similar distribution characteristics of inhaled allergens.

[Mechanism and Clinical Significance of NAMPT in Multiple Myeloma].

OBJECTIVE: To investigate the mechanism and clinical value of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM). METHODS: RT-qPCR and Western blot were used to detect the expression of NAMPT in MM cells and normal bone marrow mononuclear cells. The biological function of NAMPT was analyzed by cell proliferation and apoptosis assay, small interfering RNA silencing, overexpression assay and chromatin immunoprecipitation assay. RESULTS: The mRNA and protein expression levels of NAMPT in MM cell lines (MM1R, MM1S, U266 and RPMI-8226) were significantly higher than those in normal bone marrow mononuclear cells (P < 0.001), and were most obvious in U266 cells. Compared with Si-NC group, the proliferation of U266 cells in Si-NAMPT group was significantly inhibited at 24, 48 and 72 h after transfection (P =0.006, P < 0.001, P =0.001), and the apoptosis rate of U266 cells was significantly increased at 48 h after transfection (P < 0.001). Compared with Flag-NC group, U266 cell proliferation in Flag-NAMPT group was significantly increased (P =0.003, P =0.002, P < 0.001), while the apoptosis rate decreased significantly at 48 h after transfection. The expression of NAMPT in U266 cells was regulated by XBP1 at transcriptional level. The proliferation rate of U266 cells with XBP1 or NAMPT stable knockout or MKC3946 pretreated with bortezomib was significantly decreased, the levels of BCL-2 mRNA and protein were also significantly decreased, while the levels of BAX mRNA and protein were significantly increased, moreover, the cleavage degree of caspase-3 significantly decreased, while caspase-3/7 activity increased dramatically (P < 0.05). CONCLUSIONS: The high expression of NAMPT in MM cell line can promote MM cell proliferation and inhibit apoptosis. NAMPT is regulated by IRE1α-XBP1 signaling pathway in U266 cells. Stable knockdown of NAMPT or blocking of IRE1α-XBP1 pathway can significantly increase the sensitivity of U266 cells to bortezomib.

Pretreatment with low-frequency magnetic fields can improve the functional properties of pea globulin amyloid-like fibrils.

Plant protein fibrils have recently attracted considerable attention due to their superior mechanical and interfacial properties. The objective of this study was to evaluate the feasibility of low-frequency magnetic field (LF-MF) pretreatment in enhancing the conversion and functional characteristics of the amyloid-like fibrils derived from pea globulin (PG), which was considered a sustainable hypoallergenic protein. The results showed that LF-MF-treated PG (MPG) assembled into longer amyloid-like fibrils compared with native PG (NPG). The MPG presented similar gelling, emulsifying, and foaming properties to the NPG, while the fibril samples exhibited significantly improved functional properties. Moreover, the amyloid-like fibrils generated from the MPG (MPGF) showed large aspect ratios accompanied by superior solubility, molecular flexibility, emulsion stability, and gelling properties. The improved functional properties of the amyloid-like fibrils generated from the MPG can provide a promising outlook for expanding the applications of the PG in food, medicine and other fields.

Current and Potential Roles of Ferroptosis in Bladder Cancer.

Ferroptosis, a type of regulated cell death driven by iron-dependent lipid peroxidation, is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species. Ferroptosis is a prevalent and primitive form of cell death. Numerous cellular metabolic processes regulate ferroptosis, including redox homeostasis, iron regulation, mitochondrial activity, amino acid metabolism, lipid metabolism, and various disease-related signaling pathways. Ferroptosis plays a pivotal role in cancer therapy, particularly in the eradication of aggressive malignancies resistant to conventional treatments. Multiple studies have explored the connection between ferroptosis and bladder cancer, focusing on its incidence and treatment outcomes. Several biomolecules and tumor-associated signaling pathways, such as p53, heat shock protein 1, nuclear receptor coactivator 4, RAS-RAF-MEK, phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin, and the Hippo-tafazzin signaling system, exert a moderating influence on ferroptosis in bladder cancer. Ferroptosis inducers, including erastin, artemisinin, conjugated polymer nanoparticles, and quinazolinyl-arylurea derivatives, hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment. Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer. In this review, we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

Mixed ionic-electronic conduction in Ruddlesden-Popper and Dion-Jacobson layered hybrid perovskites with aromatic organic spacers.

The understanding of mixed ionic-electronic conductivity in hybrid perovskites has enabled major advances in the development of optoelectronic devices based on this class of materials. While recent investigations revealed the potential of using dimensionality effects for various applications, the implication of this strategy on mixed conductivity is yet to be established. Here, we present a systematic analysis of mixed conduction in layered (2D) hybrid halide perovskite films based on 1,4-phenylenedimethylammonium (PDMA) and benzylammonium (BzA) organic spacers in (PDMA)PbI4 and (BzA)2PbI4 compositions, forming representative Dion-Jacobson (DJ) and Ruddleson-Popper (RP) phases, respectively. Electrochemical measurements of charge transport parallel to the layered structure reveal mixed ionic-electronic conduction with electronic transport mediated by electron holes in both DJ and RP phases. In comparison to the 3D perovskites, larger activation energies for both ionic and electronic conductivities are observed which result in lower absolute values. While the layered perovskites still allow for a relatively efficient exchange of iodine with the gas phase, the lower change of conductivity on the variation of the iodine partial pressure compared with 3D perovskites is consistent with the exchange affecting only a fraction of the film, with implications for the encapsulating efficacy of these materials. We complement the analysis with a demonstration of the superior thermal stability of DJ structures compared to their RP counterparts. This can guide future explorations of dimensionality and composition to control the transport and stabilization properties of 2D perovskite films.

A ScWIP5 gene confers fall armyworm resistance by reducing digestive enzyme activities in sugarcane.

BACKGROUND: The fall armyworm, Spodoptera frugiperda, is one of the most dangerous pests to various crops. As the most crucial sugar crop, sugarcane is also constantly threatened by these pests. Plant wound-induced proteinase inhibitors (WIP) are natural defense proteins that play important roles in the defense system against insect attack. Breeding for resistance would be the best way to improve the variety characteristics and productivity of sugarcane. Screening and verification for potential plant endogenous insect-resistant genes would greatly improve the insect-resistant breeding progress of sugarcane. RESULTS: A sugarcane WIP5 gene (ScWIP5) was up-regulated 536 times after insect feeding treatment on previous published transcriptome databases. ScWIP5 was then cloned and its potential role in sugarcane resistance to fall armyworm evaluated by construction of transgenic Nicotiana benthamiana. The toxicity of ScWIP5 transgenic N. benthamiana to fall armyworm showed lower weight gain and higher mortality compared to wild-type N. benthamiana feeding group. Furthermore, the concentration of JA and NbAOC, NbAOS, and NbLOX from the Jasmin acid biosynthesis pathway was significantly induced in ScWIP5 transgenic N. benthamiana compared to the control. In addition, digestive enzyme actives from the insect gut were also evaluated, and trypsin and cathepsin were significantly lower in insects fed with ScWIP5 transgenic N. benthamiana. CONCLUSION: These results indicate that ScWIP5 might enhance insect resistance by increasing JA signal transduction processes and reducing insect digestive enzyme activities, thus impacting insect growth and development. © 2023 Society of Chemical Industry.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy: A case report and review of literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of death due to its complexity, heterogeneity, rapid metastasis and easy recurrence after surgical resection. We demonstrated that combination therapy with transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), Epclusa, Lenvatinib and Sintilimab is useful for patients with advanced HCC. CASE SUMMARY: A 69-year-old man who was infected with hepatitis C virus (HCV) 30 years previously was admitted to the hospital with abdominal pain. Enhanced computed tomography (CT) revealed a low-density mass in the right lobe of the liver, with a volume of 12.9 cm × 9.4 cm × 15 cm, and the mass exhibited a "fast-in/fast-out" pattern, with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL. Therefore, he was judged to have advanced HCC. During treatment, the patient received three months of Epclusa, three TACE treatments, two HAIC treatments, three courses of sintilimab, and twenty-one months of lenvatinib. In the third month of treatment, the patient developed severe side effects and had to stop immunotherapy, and the Lenvatinib dose had to be halved. Postoperative pathological diagnosis indicated a complete response. The patient recovered well after the operation, and no tumor recurrence was found. CONCLUSION: Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect. Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Experimental study on the effect and mechanism of adipose stem cell-derived exosomes combined with botulinum toxin A on skin trauma in rats.

BACKGROUND: Adipose stem cell-derived exosomes (ADSC-EXO) and botulinum toxin type A (BTX-A) individually showed a therapeutic effect on skin wound repair. AIMS: This study investigated their synergistic effect on promoting skin wound healing in vitro and in vivo and the underlying molecular events. METHODS: ADSCs were isolated from Sprague-Dawley (SD) rats to obtain ADSC-EXO by ultrafiltration and ultracentrifugation and were confirmed using nanoparticle tracking analysis and transmission electron microscopy. Human skin fibroblasts (HSF) were cultured and treated with or without ADSC-EXO, BTX-A, or their combination. Changes in cell phenotypes and protein expression were analyzed using different in vitro assays, and a rat skin wound model was used to assess their in vivo effects. RESULTS: The isolated ADSC-EXO from primarily cultured ADSCs had a circular vesicle shape with a 30-180 nm diameter. Treatment of HSF with ADSC-EXO and/or BTX-A significantly accelerated HSF migration in vitro and skin wound healing in a rat model. Moreover, ADSC-EXO plus BTX-A treatment dramatically induced VEGFA expression but reduced COL III and COL I levels in vivo. ADSC-EXO and/or BTX-A treatment significantly upregulated TGF-ß3 expression on Day 16 after surgery but downregulated TGF-ß1 expression, suggesting that ADSC-EXO plus BTX-A promoted skin wound healing and reduced inflammatory cell infiltration. CONCLUSIONS: The ADSC-EXO plus BTX-A treatment demonstrated a synergistic effect on skin wound healing through upregulation of VEGF expression and the TGF-ß3/TGF-ß1 and COL III/COL I ratio.