Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Nitrogen and Nod factor signaling determine Lotus japonicus root exudate composition and bacterial assembly.

Symbiosis with soil-dwelling bacteria that fix atmospheric nitrogen allows legume plants to grow in nitrogen-depleted soil. Symbiosis impacts the assembly of root microbiota, but it is unknown how the interaction between the legume host and rhizobia impacts the remaining microbiota and whether it depends on nitrogen nutrition. Here, we use plant and bacterial mutants to address the role of Nod factor signaling on Lotus japonicus root microbiota assembly. We find that Nod factors are produced by symbionts to activate Nod factor signaling in the host and that this modulates the root exudate profile and the assembly of a symbiotic root microbiota. Lotus plants with different symbiotic abilities, grown in unfertilized or nitrate-supplemented soils, display three nitrogen-dependent nutritional states: starved, symbiotic, or inorganic. We find that root and rhizosphere microbiomes associated with these states differ in composition and connectivity, demonstrating that symbiosis and inorganic nitrogen impact the legume root microbiota differently. Finally, we demonstrate that selected bacterial genera characterizing state-dependent microbiomes have a high level of accurate prediction.

The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro.

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.

Spectral characterization of the impact of modifiers and different prepare temperatures on snow lotus medicinal residue-biochar and dissolved organic matter.

This study involved the production of 20 biochar samples derived from secondary medicinal residues of Snow Lotus Oral Liquid, processed within the temperature range of 200-600 °C. Additionally, four medicinal residues, including dissolved organic matter (DOM), from 24 samples obtained using the shaking method, served as the primary source material. The investigation focused on two key factors: the modifier and preparation temperature. These factors were examined to elucidate the spectral characteristics and chemical properties of the pharmaceutical residues, biochar, and DOM. To analyze the alterations in the spectral attributes of biochar and medicinal residues, we employed near-infrared spectroscopy (NIR) in conjunction with Fourier-infrared one-dimensional and two-dimensional correlation spectroscopy. These findings revealed that modifiers enhanced the aromaticity of biochar, and the influence of preparation temperature on biochar was diminished. This observation indicates the stability of the aromatic functional group structure. Comparative analysis indicated that Na2CO3 had a more pronounced structural effect on biochar, which is consistent with its adsorption properties. Furthermore, we utilized the fluorescence indices from UV-visible spectroscopy and excitation-emission-matrix spectra with the PARAFAC model to elucidate the characteristics of the fluorescence components in the DOM released from the samples. The results demonstrated that the DOM released from biochar primarily originated externally. Aromaticity reduction and increased decay will enhance the ability of the biochar to bind pollutants. Those results confirmed the link between the substantial increase in the adsorption performance of the high-temperature modified charcoal in the previous study and the structural changes in the biochar. We investigated the structural changes of biochar and derivative DOM in the presence of two perturbing factors, modifier and preparation temperature. Suitable modifiers were selected. Preparation for the study of adsorption properties of snow lotus medicinal residues.

Effect of norepinephrine reuptake inhibitors combined antimuscarinic agents versus monotherapy for OSA: a systematic review and meta-analysis.

STUDY OBJECTIVES: Randomized controlled trials have shown that combining norepinephrine reuptake inhibitors and antimuscarinics can ameliorate the severity of obstructive sleep apnea (OSA). This article explores whether the effectiveness and safety of combining norepinephrine reuptake inhibitors with antimuscarinic agents surpass monotherapy for treating OSA. METHODS: We searched the randomized controlled trials (RCTs) with adult patients of OSA who received combination and monotherapy in eight databases from inception until April 5, 2023, next evaluated the included studies' quality, and conducted a meta-analysis and systematic review. The primary outcome was the apnea-hypopnea index (AHI). Secondary outcome measures included loop gain, hypoxic load, oxygen desaturation index, and Vpassive, among other indicators. We assessed the quality of the studies using Cochrane Methods criteria. RESULTS: Identifying four RCTs for systematic review and two for meta-analysis. The results of the meta-analysis showed that norepinephrine reuptake inhibitors combined with antimuscarinic agents in patients with OSA prolonged total sleep time by a mean of 28.20 min [95% CI (5.78, 50.61), P = 0.01], increased sleep efficiency by 4.73% [95%CI (0.50, 8.97), P = 0.03] compared with norepinephrine reuptake inhibitors alone. Other indices and adverse events were no statistical significance. The systematic reviews revealed that norepinephrine reuptake inhibitors combined with antimuscarinics may be superior to monotherapy in improving AHI and endotypic traits. CONCLUSIONS: This article demonstrated the potential advantages of combining norepinephrine reuptake inhibitors plus antimuscarinics for treating OSA, contrasting with the norepinephrine reuptake inhibitors alone, and revealed no statistically significant safety.

Quantifying peripapillary vessel density and retinal nerve fibre layer in type 1 diabetic children without clinically detectable retinopathy using OCTA.

AIM: To quantify changes in radial peripapillary capillary vessel density (ppVD) and the peripapillary retinal nerve fiber layer (pRNFL) in children with type 1 diabetes without clinical diabetic retinopathy by optical coherence tomography angiography (OCTA), providing a basis for early retinopathy in children with type 1 diabetes. METHODS: This was a retrospective study. A total of 30 patients (3-14y) with type 1 diabetes without clinical diabetic retinopathy (NDR group) were included. A total of 30 age-matched healthy subjects were included as the normal control group (CON group). The HbA1c level in the last 3mo was measured once in the NDR group. The pRNFL thickness and ppVD were automatically measured, and the mean pRNFL and ppVD were calculated in the nasal, inferior, temporal, and superior quadrants. The changes in ppVD and pRNFL in the two groups were analyzed. RESULTS: Compared with CON group, the nasal and superior ppVDs decreased in the NDR group (all P<0.01). The thickness of the nasal pRNFL decreased significantly (P<0.01), while the inferior, temporal and superior pRNFLs slightly decreased but not significant in the NDR group (all P>0.05). Person and Spearman correlation analysis of ppVD and pRNFL thickness in each quadrant of the NDR group showed a positive correlation between nasal and superior (all P<0.01), while inferior and temporal had no significant correlation (all P>0.05). There was no significant correlation between the HbA1c level and ppVD and pRNFL in any quadrant (all P>0.05). There was no significant correlation between the course of diabetes mellitus and ppVD and pRNFL in any quadrant (all P>0.05). CONCLUSION: ppVD and pRNFL decrease in eyes of children with type 1 diabetes before clinically detectable retinopathy and OCTA is helpful for early monitoring．.

Data mining and analysis of adverse event signals associated with teprotumumab using the Food and Drug Administration adverse event reporting system database.

BACKGROUND: Teprotumumab was approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease in 2020. However, its adverse events (AEs) have not been investigated in real-world settings. AIM: This study aimed to detect and evaluate AEs associated with teprotumumab in the real-world setting by conducting a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database. METHOD: Reporting odds ratio (ROR) was used to detect risk signals from the data from January 2020 to March 2023 in the FAERS database. RESULTS: A total of 3,707,269 cases were retrieved, of which 1542 were related to teprotumumab. The FAERS analysis identified 99 teprotumumab-related AE signals in 14 System Organ Classes (SOCs). The most frequent AEs were muscle spasms (n = 287), fatigue (n = 174), blood glucose increase (n = 121), alopecia (n = 120), nausea (n = 118), hyperacusis (n = 117), and headache (n = 117). The AEs with strongest signal strengths were autophony (ROR = 14,475.49), deafness permanent (ROR = 1853.35), gingival recession (ROR = 190.74), deafness neurosensory (ROR = 129.89), nail growth abnormal (ROR = 103.67), onychoclasis (ROR = 73.58), ear discomfort (ROR = 72.88), and deafness bilateral (ROR = 62.46). Eleven positive AE signals were found at the standardized MedDRA queries (SMQs) level, of which the top five SMQs were hyperglycemia/new-onset diabetes mellitus, hearing impairment, gastrointestinal nonspecific symptoms and therapeutic procedures, noninfectious diarrhea, and hypertension. Age significantly increased the risk of hearing impairment. CONCLUSION: This study identified potential new and unexpected AE signals of teprotumumab. Our findings emphasize the importance of pharmacovigilance analysis in the real world to identify and manage AEs effectively, ultimately improving patient safety during teprotumumab treatment.

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

BACKGROUND: Intracellular Ca2+ cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) is responsible for the sequestration of cytosolic Ca2+ into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear. METHODS: Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20flox mice with Myh6-Cre mice. Echocardiography, blood pressure measurements, Langendorff perfusion, histological analysis and immunohistochemistry, quantitative reverse transcription-PCR, Western blot analysis, electrophysiological measurements, and chromatin immunoprecipitation assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Specific ablation of ZBTB20 in cardiomyocyte led to a significant increase in basal myocardial contractile parameters both in vivo and in vitro, accompanied by an impairment in cardiac reserve and exercise capacity. Moreover, the cardiomyocytes lacking ZBTB20 showed an increase in sarcoplasmic reticular Ca2+ content and exhibited a remarkable enhancement in both SERCA2a activity and electrically stimulated contraction. Mechanistically, PLN expression was dramatically reduced in cardiomyocytes at the mRNA and protein levels by ZBTB20 deletion or silencing, and PLN overexpression could largely restore the basal contractility in ZBTB20-deficient cardiomyocytes. CONCLUSIONS: These data point to ZBTB20 as a fine-tuning modulator of PLN expression and SERCA2a activity, thereby offering new perspective on the regulation of basal contractility in the mammalian heart.

Leukocyte immunoglobulin-like receptor A3 gene deletion in five Chinese populations and protective association with nasopharyngeal carcinoma.

Among the thirteen leukocyte Ig-like receptor (LILR) loci located at 19q13.4, LILRA3 is unique in that it encodes a soluble protein lacking the transmembrane and cytoplasmic domains, and a 6.7 kb deletion spanning the first seven exons has been detected in some human individuals. Presently, there is a lack of data about the distribution of LILRA3 gene deletion in more diverse ethnic groups. Also, no previous studies have investigated the correlation between copy number variation (CNV) of LILRA3 and nasopharyngeal carcinoma (NPC). In this study, five populations from China mainland: two Southern Han populations, Hunan (N = 1478) and Guandong (N = 107); one Southeastern Han population, Fujian (N = 439); and two Northern populations, Inner Mongolia Han (N = 104) and Mongol population from Inner Mongolia (N = 158) were investigated for CNV of LILRA3 using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. LILRA3 variants were also examined in a cohort of NPC cases (N = 1142) in Hunan Han population. The five Chinese populations demonstrated northward increase in frequency of the deleted form of LILRA3 gene (LILRA3*Del) (all corrected p values < 0.05). Inter-population comparison also uncovered significant differentiation in the distribution of CNV of LILRA3 among modern human populations. LILRA3*Del was found to confer significantly reduced risk to NPC in Hunan Han population (at allelic level: OR = 0.79, 95% CI = 0.71-0.89, p < 0.0001; at genotype level: OR = 0.63, 95% CI = 0.51-0.79, p < 0.0001). No interaction was found between LILRA3 variants and HLA-A*02:07, HLA-A*11:01, HLA-B*13 and HLA-B*46:01 alleles in susceptibility to NPC. Our study constitutes the first demonstration of LILRA3 gene as a locus linked to NPC susceptibility in a southern Chinese population. Future independent studies in other populations are warranted to confirm the findings reported in this study.

Advances in the use of local anesthetic extended-release systems in pain management.

Pain management remains among the most common and largely unmet clinical problems today. Local anesthetics play an indispensable role in pain management. The main limitation of traditional local anesthetics is the limited duration of a single injection. To address this problem, catheters are often placed or combined with other drugs in clinical practice to increase the time that local anesthetics act. However, this method does not meet the needs of clinical analgesics. Therefore, many researchers have worked to develop local anesthetic extended-release types that can be administered in a single dose. In recent years, drug extended-release systems have emerged dramatically due to their long duration and efficacy, providing more possibilities for the application of local anesthetics. This paper summarizes the types of local anesthetic drug delivery systems and their clinical applications, discusses them in the context of relevant studies on local anesthetics, and provides a summary and outlook on the development of local anesthetic extended-release agents.

First report of leaf spot disease caused by Alternaria alternata on Polygonatum cyrtonema Hua in Hunan Province of China.

Polygonatum cyrtonema Hua, a perennial plant of the Asparagaceae family, is an important herb in Chinese medicine and is mainly grown in the Chinese provinces of Guizhou, Hunan, Yunnan, Anhui, and Zhejiang (Chen et al. 2021). In June 2021, a new case of leaf spot disease was detected in an 80 m2 plantation of P. cyrtonema on Xuefeng Mountain, Huaihua City, Hunan Province (27°17'30″N, 110°24'20″E). It infected almost 40% of the total planted area. Initially, irregular light brown spots appeared on the leaves, gradually turning dark brown and coalescing to form large necrotic areas, after which the affected plant turned yellow and eventually died. Ten disease samples were collected from ten plants in the plantation area. The leading edge of necrotic tissues were rinsed with sterile water and then disinfected with 3% hydrogen peroxide for 30 s, followed by 75% ethanol for 90 s, and rinsed three times with sterile water. Samples were then placed on water agar plates and incubated in the dark in a constant temperature incubator at 28 ℃ for 3-5 days. After mycelial growth was observed in the media, the hyphae were transferred to potato dextrose agar plates and incubated for 3-5 days at 28 ℃ in the dark. Ultimately, 12 purified fungal isolates were obtained, some of which were morphologically similar, including 10 that were Alternaria (83.3% isolation rate). Three representative isolates (HJYB1, HJYB2, and HJYB3) were selected for further study. The initial colonies were grayish green with white fluffy mycelia on the surface and a prominent white rim, which became brown with dense, cottony aerial mycelia as the colonies matured. The conidia were obpyriform or ellipsoidal, pale to dark brown, with 0-4 transverse and 0-3 longitudinal septa, some with a short cylindrical beak at the tip. They measured 11.826-28.873 × 6.231-26.018 µm (n = 100). To further confirm the identity of the isolates, their rDNA internal transcribed spacer region (ITS), ß-microtubulin (TUB2) and translation elongation factor-1 (TEF-1) genes were amplified and sequenced using the ITS4/ITS5, TUB2F/R and EF-526F/1567R primers, respectively (Hong et al. 2006). The sequences were submitted to GenBank (ITS: OR513924, OR513964, OR519874; TUB2: OR526928, OR533421, OR526929; TEF: OR526926, OR533420, OR526927). A concatenated phylogenetic tree of the three genes showed that the isolate clustered significantly with Alternaria alternata. Based on morphological identification and phylogenetic tree analysis, the isolate was identified as A. alternata. We carried out pathogenicity tests on four uniformly growing P. cyrtonema plants. Three of these plants were used as experimental plants and one as a control. For each plant, three young leaves were selected and inoculated with 6 × 6 mm PDA blocks, while sterile PDA blocks were used as controls. The treated plants were subjected to 10 days of stable temperature in a climatic chamber set at 28°C, 80% constant relative humidity and 12 hours of light per day. The pathogenic lesions appeared and the pathogens re-isolated from the diseased leaves showed similar morphological characteristics to representative isolates and were confirmed as A. alternata by DNA sequencing, thus fulfilling Koch's postulates. A. alternata is the major causal agent of leaf spot on P. sibiricum (Zou et al. 2023) and Agrimonia pilosa (Jiang et al. 2023). As far as we know, leaf necrosis caused by A. tenuissima has been found on P. cyrtonema (Li et al. 2020). To our knowledge, this is the first report of A. alternata causing leaf spot disease in P. cyrtonema. These findings form the basis for the management of this leaf spot disease.

[Distribution Characteristics and Environmental Driving Factors of Cyanobacteria Community in Impounded Lakes and Reservoirs in Shandong on the East Route of South-to-North Water Diversion Project].

To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa, and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa, and M. wesenbergii. The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa, and M. wesenbergii had growth advantages when the water temperature was higher than 25℃. In addition, shallow water was more conducive to the growth of C. raciborskii. It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.

Sensorineural hearing loss induced by gefitinib: A CARE-compliant case report and literature reviews.

RATIONALE: Gefitinib is a potent and selective orally active growth factor receptor (EGFR)-tyrosine kinase inhibitor that is commonly used to treat advanced non-small cell lung cancer patients with activating EGFR mutations. Hearing impairment with gefitinib was sparsely reported. In this report, we describe a case of sensorineural deafness associated with the administration of gefitinib, with a Naranjo score of 7. PATIENT CONCERNS: An 81-year-old female was diagnosed with lung adenocarcinoma with bone metastasis and an EGFR-activating mutation. The patient was prescribed gefitinib tablets at a daily dose of 250 mg for lung adenocarcinoma treatment. However, the patient experienced moderate to severe bilateral sensorineural deafness, primarily in her right ear, after taking gefitinib. Following the cessation of gefitinib administration, the patient exhibited partial restoration of auditory function. Upon resuming the medication, she experienced a worsening of deafness. DIAGNOSES: The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness. INTERVENTIONS: The otolaryngologist recommended bilateral hearing aids to enhance hearing function. OUTCOMES: Throughout our follow-up period, the patient did not receive a hearing aid implant. LESSONS: This article first reported the ototoxicity caused by gefitinib. While rare, our report highlights that gefitinib-induced sensorineural deafness is possible and its mechanisms are still unclear. This adverse reaction should be monitored closely during clinical application of gefitinib to improve patient outcomes.

Y-box protein-1 modulates circSPECC1 to promote glioma tumorigenesis via miR-615-5p/HIP1/AKT axis.

Y-box binding protein-1 (YB-1) is upregulated in glioma and plays an important role in its occurrence and drug resistance. However, the involved regulatory processes and downstream pathways are still unclear. Since various circular RNAs (circRNAs) and microRNAs (miRNAs) also play roles in the pathogenesis of glioma, we hypothesize that YB-1 may exert its function through a circRNA-miRNA-protein interaction network. In this study, we use the RNA binding protein immunoprecipitation assay and quantitative reverse transcription polymerase chain reaction to determine the circRNAs involved in the regulation of YB-1 and further elucidate their biological functions. The level of circSPECC1 (hsa_circ_0000745) modulated by YB-1 is significantly upregulated in the U251 and U87 glioma cell lines. Downregulation of circSPECC1 markedly inhibits the proliferation and invasiveness of U251 and U87 cells by inducing apoptosis. Bioinformatics analysis reveals that miR-615-5p could interact with circSPECC1 and huntingtin-interacting protein-1 (HIP-1). Then we determine the interactions between miR-615-5p, circSPECC1, and HIP1 using dual luciferase reporter system and pull-down assays. Mechanistic analysis indicates that the downregulation of circSPECC1 results in a decreased HIP1 expression. This study demonstrates that circSPECC1 modulated by YB-1 is increased in glioma cell lines. In addition, circSPECC1 promotes glioma growth through the upregulation of HIP1 by sponging miR-615-5p and targeting the HIP1/AKT pathway. This indicates that YB-1 and circSPECC1 may both be promising targets for glioma treatment.

Preliminary study of 3D printing technology for extracorporeal positioning guide assisted ultrasound-guided microwave ablation of the liver.

BACKGROUND: We designed a 3D-printed extracorporeal positioning guide for assisting ultrasound-guided microwave ablation of the liver and observed its effectiveness. RESEARCH DESIGN AND METHODS: 13 patients with liver cancer were selected, and their CT data were obtained. The CT data is reconstructed in 3D by computer software Mimics to create a 3D model. The 3D-printed in vitro positioning guides were designed by 3-Matic and fabricated using 3D printing technology. Finally, it is applied to the clinic, and its effect is observed. RESULTS: The preliminary design of a 3D printed extracorporeal positioning guide was applied to the clinic, and the efficiency of assisted ultrasound positioning was 76.92% (10/13), with three patients requiring repositioning. The efficiency of the 3D printed extracorporeal positioning guide technique was 76.92%, a CT examination was performed one month after surgery, and three patients had residual lesions. CONCLUSIONS: 3D-printed extracorporeal positioning guides can assist ultrasound in localizing tumors during liver microwave ablation and reduce repeated punctures. It makes percutaneous microwave ablation of the liver more precise and safe. However, the current study sample is small, there are still apparent shortcomings, and long-term clinical studies are needed to prove its effectiveness.

Maternal Supplementary Tapioca Polysaccharide Iron Improves the Growth Performance of Piglets by Regulating the Active Components of Colostrum and Cord Blood.

The purpose of this study was to investigate the effect of maternal supplementation with TpFe (tapioca polysaccharide iron) on reproductive performance, colostrum composition, cord blood active components of sows, and growth performance of their nursing piglets. Sixty healthy Duroc × Landrace × Yorkshire sows were randomly assigned to three groups at day 85 of gestation. The experimental diets included a basal diet supplemented with 100 mg/kg FeSO4·H2O (CON group), the basal diet supplemented with 50 mg/kg TpFe (TpFe50 group), and the basal diet supplemented with 100 mg/kg TpFe (TpFe100 group), as calculated by Fe content. The experiment lasted from day 85 of gestation to the end of weaning (day 21 of lactation). Results showed that maternal supplementation with 100 mg/kg TpFe improved (p < 0.05) feed intake during lactation, live births, and birth weight of the litter (alive) and increased (p < 0.05) colostrum IgM (immunoglobulin m), IgA (immunoglobulin A), as well as the IgG levels, while it decreased (p < 0.05) the urea nitrogen and somatic cell count of sows. Moreover, sows in the TpFe100 group had higher (p < 0.05) serum iron levels and IgG. Additionally, maternal supplementation with 100 mg/kg TpFe increased (p < 0.05) iron level, total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-px), catalase (CAT), IgG, red blood cells (RBC), and hemoglobin (Hb) of cord blood, similar with the iron content, T-AOC, GSH-px, IgG, RBC, Hb, hematocrit (HCT), and mean corpuscular volume (MCV) of weaned piglet blood. The diarrhea and mortality rates among the nursing piglets were decreased (p < 0.05), while the average weight at day 21 of age was increased (p < 0.05) in the TpFe100 group. Serum PRL (prolactin) levels of sows exhibited a positive correlation (p < 0.05) with live births. Suckling piglet diarrhea was positively correlated with colostrum urea nitrogen level but negatively correlated with colostrum IgM, IgG, and cord blood Hb content (p < 0.05). The mortality of suckling piglets was negatively correlated with serum iron content and IgM in colostrum, GSH-px, and IgG in cord serum of sows (p < 0.05). The average weight of weaning piglets was positively (p < 0.05) related to colostrum IgM and IgG levels, as well as cord serum RBC counts of sows on day 21. In conclusion, maternal supplementation with TpFe can improve the active components of colostrum and umbilical cord blood and improve the growth performance of suckling piglets.

Effect of sodium-glucose transporter 2 inhibitors on sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Objective: Sarcopenia has been recognized as the third category of disabling complications in patients with type 2 diabetes mellitus(T2DM), in addition to micro- and macrovascular complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are innovative glucose-lowering treatments that have been shown to reduce body weight and enhance cardiovascular and renal outcomes. However, there is vigilance that SGLT2 inhibitors should be taken cautiously because they target skeletal muscle and may raise the risk of sarcopenia. Herein, we conducted a meta-analysis of randomized controlled trials to evaluate the effects of SGLT2 inhibitors on sarcopenia in patients with T2DM. Method: Relevant studies were obtained from PubMed, Embase, Medicine, Cochrane, and Web of Science databases to determine eligible studies until February 2023, without any language restrictions. A random effects model was utilized irrespective of heterogeneity, and the I2 statistic was used to evaluate study heterogeneity. The differences in results were measured using the weighted average difference (WMD) of the continuous data, along with a 95% confidence interval (CI). Results: A total of 25 randomized controlled trials with 2,286 participants were included. SGLT2 inhibitors significantly reduced weight-related changes and fat-related changes, including body weight(BW) (WMD= -2.74, 95% CI: -3.26 to -2.23, P<0.01), body mass index(BMI) (WMD= -0.72, 95% CI: -0.95 to -0.49, P<0.01), waist circumference(WC) (WMD= -1.60, 95% CI: -2.99 to -0.22, P=0.02), fat mass(FM)(WMD= -1.49, 95% CI: -2.18 to -0.80, P<0.01), percentage body fat(PBF) (WMD= -1.28, 95% CI: -1.83 to -0.74, P<0.01), visceral fat area(VFA)(WMD= -19.52, 95% CI: -25.90 to -13.14, P<0.01), subcutaneous fat area(SFA)(WMD= -19.11, 95% CI: -31.18 to -7.03, P=0.002), In terms of muscle-related changes, lean mass(LM)(WMD= -0.80, 95% CI: -1.43 to -0.16, P=0.01), and skeletal muscle mass(SMM) (WMD= -0.38, 95% CI: -0.65 to -0.10, P=0.007), skeletal muscle index(SMI) (WMD= -0.12, 95% CI: -0.22 to -0.02, P=0.02)were also significantly reduced. In addition, body water likewise decreased significantly (WMD=-0.96, 95% CI: -1.68 to -0.23, P=0.009). Conclusions: As one of the most widely used hypoglycemic, SGLT2 inhibitors have beneficial effects on FM and BW weight loss in T2DM, such as BW, BMI, WC, FM, PBF, VFA, and SFA. However, the negative influence on muscle mass paralleled the reduction in FM and BW, and the consequent increased risk of sarcopenia warrants high attention, especially as patients are already predisposed to physical frailty. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier PROSPERO (No.CRD 42023396278).

Bacterial co-infection raises in-hospital mortality of COVID-19 patients: a retrospective study.

Background: We aim to explore whether the bacterial co-infection with COVID-19 will raise the in-hospital mortality. Methods: COVID-19 patients' information were collected for analysis in our retrospective study. Neutrophil count and procalcitonin (PCT) were used to estimate whether there was a suspected bacterial co-infection. Results: The main baselines between the suspected bacterial infection (SBI) and no evidence of bacterial infection (NBI) groups were no significant differences. In SBI group, patients required more therapies than NBI group. There was significantly higher in-hospital mortality (26% vs.9%, P < 0.001) between SBI and NBI groups in overall population. And in each subgroup based on pneumonia inflammation index (PII), it also showed higher in-hospital mortality of COVID-19 patients with bacterial co-infection. With logistic regression models, it showed that bacterial co-infection was associated with significantly higher in-hospital mortality in overall population (OR 1.694, 95% CI 1.179-2.434, p = 0.004) and mild subgroup (OR 2.374, 95% CI 1.249-4.514, p = 0.008). The rate of bacterial co-infection in overall population was 51%. At the same time, it showed a significantly higher rate of bacterial co-infection in critical subgroup than severe subgroup (63% vs. 49%, p = 0.003), and than that in moderate subgroup (63% vs. 48%, p = 0.002) based on clinical classification. It showed a significantly higher rates of bacterial co-infection in severe subgroup than moderate subgroup (66% vs. 49%, p = 0.001) based on PII. The result showed that the risk factor associated with significantly higher in-hospital mortality was PII (OR 1.018, 95%CI 1.012 to 1.024, P < 0.001) with logistic regression models. Interpretation: Bacterial co-infection estimated by Neutrophil count and procalcitonin significantly raises in-hospital mortality of COVID-19 patients in overall population in our study. Its impact is more significant in mild and moderate PII subgroups. PII based on CT imaging combined with neutrophil count and PCT is beneficial for accurate differentiation of bacterial co-infection of COVID-19.

First Report of Tomato spotted wilt virus infecting Helichrysum bracteatum in China.

Strawflower (Helichrysum bracteatum, Asteraceae) , an annual or biennial herb, is one of the most popular flowers in the world because of the colorful flowers and the long flowering period. However, the ornamental plants belonging to Asteraceae are susceptible to numerous viruses such as cucumber mosaic virus (CMV) (Cucumovirus, Bromoviridae) , potato virus Y (Potyvirus, Potyviridae), tomato mosaic virus (ToMV) (Tobamovirus, Virgaviridae), tobacco mosaic virus (TMV) (Tobamovirus, Virgaviridae), chrysanthemum virus B (CVB) (Carlavirus, Betaflexiviridae), tomato aspermy virus (TAV) (Cucumovirus, Bromoviridae), tomato spotted wilt virus (TSWV) (Orthotospovirus tomatomaculae, Tospoviridae), and impatiens necrotic spot virus (INSV) (Orthotospovirus impatiensnecromaculae, Orthotospovirus) resulting in severe yield loss (Verma et al. 2003; Raj et al. 2007; Kondo et al. 2011; Liu et al. 2014; Marys et al. 2014; Min et al. 2020; Gautam et al. 2021; Read et al. 2022; Supakitthanakorn et al. 2022). Among these viruses, the TSWV, a thrips-transmitted negative-stranded RNA virus, is well known to cause viral disease in several plant species while is less reported in Helichrysum, especially in China. In April 2021, viral attack symptoms were detected on the leaves of H. bracteatum during our routine checks in the greenhouse located at Shunyi District, Beijing, China, such as wilting, shrinking, chlorotic blotches, chlorotic ring spots. To investigate the virus infecting H. bracteatum, in total of 25 symptomatic and 5 asymptomatic leaves were sampled and tested by the effective double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) using antisera against CMV, PVY/PVX, ToMV, TMV, CVB, TAV, TSWV, INSV, separately (Agdia, USA). Only the TSWV showed positive in symptomatic samples, and asymptomatic samples were all negative, which implied TSWV infection. To further confirm the virus type of TSWV isolated from H. bracteatum samples, the genomic RNA of the virus was isolated using reverse transcription and polymerase chain reaction (RT-PCR), and then was cloned, sequenced and analyzed. Total RNA of five symptomatic leaves (ELISA-positive) were extracted using the FastPure Plant Total RNA Isolation Kit (Vazyme, China), and then were reverse transcribed by HiScript II Reverse Transcriptase (Vazyme, China). Each genome segments were amplified using Phanta Max Super-Fidelity DNA Polymerase (Vazyme, China) with TSWV-specific primers newly designed and listed in Table S1. The PCR setup was as follow: 95°C for 30 s, followed by 35 cycles at 95°C for 30 s, 55°C for 30 s, and 72°C for 1.5 min, with a final extension at 72°C for 10 min. All PCR products were cloned into the TA/Blunt-Zero vector (Vazyme, China) and sequenced (GENEWIZ, Inc.). We assembled and then analyzed the evolutionary relationship of three genomic fragments, that is, TSWV-BJFC-Hb S (2923 bp), M (4785 bp) and L (8971 bp) using the BLAST tools. The results showed high similarity with TSWV-henan isolated from pepper in China (99.6% to TSWV-S (MT799179.1), 99.8 % to TSWV-M (MT799178.1) and 99.8 % TSWV-L (MT799177.1)). These sequences have been submitted to the GenBank (OM982910, OM982911 and OM937131). Taking all of these evidences together, the viral disease observed in H. bracteatum was closely associated with TSWV. TSWV is currently widespread in China, infecting Nasturtium, Chrysanthemum and cowpea (Xiao et al. 2015; Hu et al. 2018; Yu et al. 2021). Epidemics of TSWV have also been reported in several other countries such as Korea, North Carolina, Turkey and India (Renukadevi et al. 2015; Koehler et al. 2016; Kwak et al. 2021; Erilmez, S. 2022). This is the first report of TSWV infection on H. bracteatum in China. Due to the fast spread and serious economic losses of TSWV, the rapid detection may be the essential way to prevent this viral disease among crops (Macharia et al. 2014).