Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China.

BACKGROUND: Alpha-papillomavirus 9 (α-9) is a member of the human papillomavirus (HPV) α genus, causing 75% invasive cervical cancers worldwide. The purpose of this study was to provide data for effective treatment of HPV-induced cervical lesions in Taizhou by analysing the genetic variation and antigenic epitopes of α-9 HPV E6 and E7. METHODS: Cervical exfoliated cells were collected for HPV genotyping. Positive samples of the α-9 HPV single type were selected for E6 and E7 gene sequencing. The obtained nucleotide sequences were translated into amino acid sequences (protein primary structure) using MEGA X, and positive selection sites of the amino acid sequences were evaluated using PAML. The secondary and tertiary structures of the E6 and E7 proteins were predicted using PSIPred, SWISS-MODEL, and PyMol. Potential T/B-cell epitopes were predicted by Industrial Engineering Database (IEDB). RESULTS: From 2012 to 2023, α-9 HPV accounted for 75.0% (7815/10423) of high-risk HPV-positive samples in Taizhou, both alone and in combination with other types. Among these, single-type-positive samples of α-9 HPV were selected, and the entire E6 and E7 genes were sequenced, including 298 HPV16, 149 HPV31, 185 HPV33, 123 HPV35, 325 HPV52, and 199 HPV58 samples. Compared with reference sequences, 34, 12, 10, 2, 17, and 17 nonsynonymous nucleotide mutations were detected in HPV16, 31, 33, 35, 52, and 58, respectively. Among all nonsynonymous nucleotide mutations, 19 positive selection sites were selected, which may have evolutionary significance in rendering α-9 HPV adaptive to its environment. Immunoinformatics predicted 57 potential linear and 59 conformational B-cell epitopes, many of which are also predicted as CTL epitopes. CONCLUSION: The present study provides almost comprehensive data on the genetic variations, phylogenetics, positive selection sites, and antigenic epitopes of α-9 HPV E6 and E7 in Taizhou, China, which will be helpful for local HPV therapeutic vaccine development.

Disruption of NADPH homeostasis by total flavonoids from Adinandra nitida Merr. ex Li leaves triggers ROS-dependent p53 activation leading to apoptosis in non-small cell lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Adinandra nitida Merr. ex Li leaves serve as a herbal tea and hold a significant role in traditional Chinese medicine, being applied to assist in tumor treatment. Flavonoids present the primary bioactive constituents in Adinandra nitida Merr. ex Li leaves. AIM OF THE STUDY: To explore the potential of total flavonoids from Adinandra nitida Merr. ex Li Leaves (TFAN) in inhibiting non-small cell lung cancer (NSCLC) and further elucidate the underlying mechanisms. MATERIALS AND METHODS: Human NSCLC cell lines and normal lung cell line were employed to assess the impact of TFAN (0-160 µg/mL for 24, 28 and 72 h) on cell proliferation in vitro. Immunofluorescence (IF) staining gauged p53 expression changes in NSCLC cells under TFAN present condition (150 µg/mL for 24 h). In vivo study utilized NSCLC cell derived xenograft tumors in nude mice, administering TFAN orally (200 and 400 mg/kg) for 14 days. Immunohistochemistry assessed Cleaved Caspase 3 expression change in A549 xenograft tumors treated with TFAN (400 mg/kg for 14 days). RNA-seq and KEGG analysis identified gene expression changes and enriched processes in A549 xenograft tumors treated with TFAN. CM-H2DCFDA and metabolomics assessed ROS level and GSH/GSSG pool changes in A549 cells under TFAN present condition. Cell viability assay and IF staining assessed A549 cell proliferation and p53 expression changes under H2O2-induced oxidative stress (0-40 µM for 24 h) and TFAN present conditions. GSEA and N-Acetyl-L-cysteine (NAC) rescue (0-1 µM for 24 h) analyzed the impact of TFAN on GSH de novo synthesis. NADPH/NADP+ pool measurement and NADPH rescue (0-10 µM for 24 h) analyzed the impact of TFAN on GSH salvage synthesis. GC-FID and HPLC-MS were utilized to detect ethanol and ethyl acetate residues, and to characterize the chemical constituents in TFAN, respectively. The total flavonoid content of TFAN was determined using a 330 nm wavelength. RESULTS: TFAN significantly inhibited A549 cells (wild-type p53) but not NCI-H1299 cells (p53-deficient), NCI-H596 cells (p53-mutant) or BEAS-2B in vitro. IF staining validated p53 genotype for the cell lines and revealed an increase in p53 expression in A549 cells after TFAN treatment. In vivo, TFAN selectively inhibited A549 xenograft tumor growth without discernible toxicity, inducing apoptosis evidenced by Cleaved Caspase 3 upregulation. RNA-seq and KEGG analysis suggested ROS biosynthesis was involved in TFAN-induced p53 activation in A549 cells. Elevated ROS level in TFAN-treated A549 cells were observed. Moreover, TFAN sensitized A549 cells to H2O2-induced oxidative stress, with higher p53 expression. Additionally, A549 cells compensated with GSH de novo synthesis under TFAN present condition, confirmed by GSEA and NAC rescue experiment. TFAN disrupted NADPH homeostasis to impair GSH salvage biosynthesis, supported by NADPH/NADP+ change and NADPH rescue experiment. The chemical constituents of TFAN, with acceptable limits for ethanol and ethyl acetate residues and a total flavonoid content of 68.87%, included Catechin, Epicatechin, Quercitroside, Camellianin A, and Apigenin. CONCLUSION: The disruption of NADPH homeostasis by TFAN triggers ROS-dependent p53 activation that leads to apoptotic cell death, ultimately suppressing NSCLC growth. These findings offer potential therapeutic implications of Adinandra nitida Merr. ex Li leaves in combating NSCLC.

Atomic Strain Wave-Featured LaRuIr Nanocrystals: Achieving Simultaneous Enhancement of Catalytic Activity and Stability toward Acidic Water Splitting.

Rare earth microalloying nanocrystals have gotten widespread attention due to their unprecedented performances with customization-defected nanostructures, divided energy bands, and ensembled surface chemistry, regarded as a class of ideal electrocatalysts for oxygen evolution reaction (OER). Herein, a lanthanide microalloying strategy is proposed to fabricate strain wave-featured LaRuIr nanocrystals with oxide skin through a rapid crystal nucleation, using thermally assisted sodium borohydride reduction in aqueous solution at 60 °C. The atomic strain waves with alternating compressive and tensile strains, resulting from La-stabilized edge dislocations in form of Cottrell atmospheres. In 0.5 m H2SO4, the LaRuIr displays an overpotential of 184 mV at 10 mA cm-2, running at a steadily cell voltage for 60 h at 50 mA cm-2, eightfold enhancement of IrO2||Pt/C assemble in PEMWE. The coupled compressive and tensile profiles boost the OER kinetics via faster AEM and LOM pathways. Moreover, the tensile facilitates surface structure stabilization through dynamic refilling of lattice oxygen vacancies by the adsorbed oxyanions on La, Ru, and Ir sites, eventually achieving a long-term stability. This work contributes to developing advanced catalysts with unique strain to realize simultaneous improvement of activity and durability by breaking the so-called seesaw relationship between them during OER for water splitting.

Rapid Conversion from Alloy Nanoparticles to Oxide Nanowires: Strain Wave-Driven Ru-O-Mn Collaborative Catalysis for Durable Oxygen Evolution Reaction.

Metal-doped ruthenium oxides with low prices have gained widespread attention due to their editable compositions, distorted structures, and diverse morphologies for electrocatalysis. However, the mainstream challenge lies in breaking the so-called seesaw relationship between activity and stability during acidic oxygen evolution reaction (OER). Herein, strain wave-featured Mn-RuO2 nanowires (NWs) with asymmetric Ru-O-Mn bonds are first fabricated by thermally driven rapid solid phase conversion from RuMn alloy nanoparticles (NPs) at moderate temperature (450 °C). In 0.5 M H2 SO4 , the resultant NWs display a surprisingly ultralow overpotential of 168 mV at 10 mA cm-2 and run at a stable cell voltage (1.67 V) for 150 h at 50 mA cm-2 in PEMWE, far exceeding IrO2 ||Pt/C assemble. The simultaneous enhancement of both activity and stability stems from the presence of dense strain waves composed of alternating compressive and tensile ones in the distorted NWs, which collaboratively activate the Ru-O-Mn sites for faster OER. More importantly, the atomic strain waves trigger dynamic Ru-O-Mn regeneration via the refilling of oxygen vacancies by oxyanions adsorbed on adjacent Mn and Ru sites, achieving long-term stability. This work opens a door to designing non-precious metal-assisted ruthenium oxides with unique strains for practical application in commercial PEMWE.

[Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children].

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Orange-peel derived carbon-loaded low content ruthenium nanoparticles as ultra-high performance alkaline water HER electrocatalysts.

Carbon materials have a very wide range of applications in the field of electrocatalysis, both as catalyst bodies and as excellent supports for catalysts. In this work, we obtained a graphitic-like orange-peel derived carbon (OPC) material through pre-carbonization and KOH activation strategies using discarded orange-peel as a raw material. OPC has good graphitization characteristics and a few-layer structure, making it very suitable as a support for nanoparticle catalysts. In order to compare the performance of OPC, we used commercial graphene as the benchmark, made two carbon materials uniformly loaded with ruthenium nanoparticles under the same conditions, and obtained two HER catalysts (Ru/OPC and Ru/rGO). The results indicate that Ru/OPC has excellent HER catalytic performance under alkaline conditions, not only superior to Ru/rGO, but also surpassing commercial Pt/C. In 1 M KOH; the overpotential of Ru/OPC is only 3 mV at -10 mA cm-2, greatly exceeding those of Ru/rGO (100 mV) and Pt/C (31 mV). Under high current density (j), the performance of Ru/OPC is even better; the overpotential is 79 mV and 136 mV at -100 mA cm-2 and -200 mA cm-2, respectively. More importantly, Ru/OPC also has a very high TOF and long-term stability, with a TOF of up to 10.62 H2 s-1 at an overpotential of 100 mV and almost no attenuation after 72 h of operation at -50 mA cm-2. Ru/OPC also exhibits good catalytic performance under acidic conditions, significantly superior to that of Ru/rGO. For Ru/OPC, the overpotential is 86 mV, 167 mV and 214 mV at -10 mA cm-2, -100 mA cm-2 and -200 mA cm-2, respectively. Under the same conditions, the overpotential of Ru/rGO is 143 mV, 253 mV and 306 mV at -10 mA cm-2, -100 mA cm-2 and -200 mA cm-2, respectively.

The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice.

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear. Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons. Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect. Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.

Cervical carcinogenesis risk association of HPV33 E6 and E7 genetic variations in Taizhou, Southeast China.

BACKGROUND: Human papillomavirus (HPV) 33 belongs to the Alphapapillomavirus 9 (α-9 HPV) species group, which also contains types 16, 31, 35, 52, 58 and 67. The purpose of this study was to investigate the genetic variations of HPV33 and to explore its carcinogenicity among women in Taizhou, Southeast China. METHODS: Exfoliated cervical cells were collected for HPV genotyping. Only single HPV33 infection cases were selected, and their E6 and E7 genes were sequenced using the ABI 3730xl sequencer and then analysed using MEGA X. RESULTS: From 2014 to 2020, a total of 185 single HPV33-positive specimens were successfully amplified. We obtained 15 distinct HPV33 E6/E7 variants, which were published in GenBank under accession numbers OQ672665-OQ672679. Phylogenetic analysis revealed that all HPV33 E6/E7 variants belonged to lineage A, of which 75.7% belonged to lineage A1. Compared with CIN1, the proportion of sublineage A1 in CIN2/3 was higher, but there was no significant difference (76.5% vs. 80.6%, P > 0.05). Altogether, 20 single nucleotide substitutions were identified, of which 6 were novel substitutions, including T196G (C30G), A447T, G458T (R117L), G531A, A704A, and C740T. In addition, no significant trends were observed between the nucleotide substitutions of HPV33 E6/E7 variants and the risk of cervical lesions. CONCLUSION: This study provides the most comprehensive data on genetic variations, phylogenetics and carcinogenicity of HPV33 E6/E7 variants in Southeast China to date. The data confirmed that cervical lesions among women in Taizhou are attributable to HPV33, which may be due to the high infection rate of sublineage A1 in the population.

Molecular mechanisms of hepatoprotective effect of tectorigenin against ANIT-induced cholestatic liver injury: Role of FXR and Nrf2 pathways.

Cholestatic liver injury is caused by toxic action or allergic reaction, resulting in abnormality of bile formation and excretion. Few effective therapies have become available for the treatment of cholestasis. Herein, we found that tectorigenin (TG), a natural isoflavone, showed definite protective effects on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury, significantly reversing the abnormality of plasma alanine/aspartate aminotransferase, total/direct bilirubin and alkaline phosphatase, as well as hepatic reactive oxygen species, catalase and superoxide dismutase. Importantly, the targeted metabolomic determination found that BA homeostasis could be well maintained in TG-treated cholestatic mice, especially the levels of glycocholic acid, tauromuricholic acid, taurocholic acid, taurolithocholic acid, tauroursodeoxycholic acid and taurodeoxycholic acid. Overall, primary/secondary and amidated/unamidated bile acid (BA) levels were significantly altered upon ANIT stimulation but could be restored by TG intervention to certain extents. In addition, TG boosted the expression of farnesoid x receptor (FXR), which in turn upregulated multidrug resistance protein 2 (MRP2) and bile salt export pump (BSEP) to accelerate the excretion of BA. Meanwhile, TG enhanced the expression of Nrf2 and its upstream genes PI3K/Akt and downstream target genes HO-1, NQO1, GCLC and GCLM to strengthen the antioxidant capacity. Taken together, TG plays a vital role in maintaining BA homeostasis and ameliorating cholestatic liver injury through regulating FXR-mediated BA efflux and Nrf2-mediated antioxidative pathways.

A new sesquiterpenoid from the aconitum-derived fungus Aspergillus fumigatus M1.

A new bergamotane sesquiterpenoid, fumigatanol (1), along with nine known compounds (2-10) were isolated from the Aconitum-derived fungus Aspergillus fumigatus M1. Their structures were established on the basis of extensive spectroscopic analyses, ECD experiment and NMR computational method. Antibacterial and cytotoxic activities of compound 1 were evaluated and no obvious antibacterial and cytotoxic activities were observed at concentrations of 256 µg/mL and 40.00 µM, respectively.

Identification of the Acid-Sensitive Site Critical for Chloral Hydrate (CH) Activation of the Proton-Activated Chloride Channel.

The transmembrane protein TMEM206 was recently identified as the molecular basis of the extracellular proton-activated Cl- channel (PAC), which plays an essential role in neuronal death in ischemia-reperfusion. The PAC channel is activated by extracellular acid, but the proton-sensitive mechanism remains unclear, although different acid-sensitive pockets have been suggested based on the cryo-EM structure of the human PAC (hPAC) channel. In the present study, we firstly identified two acidic amino acid residues that removed the pH-dependent activation of the hPAC channel by neutralization all the conservative negative charged residues located in the extracellular domain of the hPAC channel and some positively charged residues at the hotspot combined with two-electrode voltage-clamp (TEVC) recording in the Xenopus oocytes system. Double-mutant cycle analysis and double cysteine mutant of these two residues proved that these two residues cooperatively form a proton-sensitive site. In addition, we found that chloral hydrate activates the hPAC channel depending on the normal pH sensitivity of the hPAC channel. Furthermore, the PAC channel knock-out (KO) male mice (C57BL/6J) resist chloral hydrate-induced sedation and hypnosis. Our study provides a molecular basis for understanding the proton-dependent activation mechanism of the hPAC channel and a novel drug target of chloral hydrate.SIGNIFICANCE STATEMENT Proton-activated Cl- channel (PAC) channels are widely distributed in the nervous system and play a vital pathophysiological role in ischemia and endosomal acidification. The main discovery of this paper is that we identified the proton activation mechanism of the human proton-activated chloride channel (hPAC). Intriguingly, we also found that anesthetic chloral hydrate can activate the hPAC channel in a pH-dependent manner. We found that the chloral hydrate activates the hPAC channel and needs the integrity of the pH-sensitive site. In addition, the PAC channel knock-out (KO) mice are resistant to chloral hydrate-induced anesthesia. The study on PAC channels' pH activation mechanism enables us to better understand PAC's biophysical mechanism and provides a novel target of chloral hydrate.

Correlates of poor insight: A comparative fMRI and sMRI study in obsessive-compulsive disorder and schizo-obsessive disorder.

BACKGROUND: Despite the several researches on the correlates of insight in psychosis, less is known regarding the specificity of disease diagnosis on the relationship between insight and the correlates. The current study sought to explore the effects of insight and disease diagnosis on those in patients with obsessive-compulsive disorder (OCD) and patients with schizo-obsessive disorder (SOD). METHODS: We evaluated clinical symptoms and neurocognitions among 111 patients (including 41 OCD with good insight, 40 OCD with poor insight, 14 SOD with good insight and 16 SOD with poor insight. Gray matter volume and spontaneous neural activity were also examined by analyzing the voxel-based morphometry and amplitude of low frequency fluctuation (ALFF), respectively. RESULTS: Interactive effects of insight and diagnosis was found on working memory and the gray matter volume in right superior and middle temporal gyrus. Main effect of insight was found on working and visual memory, compulsion and obsession, and ALFF in right middle and superior occipital cortex. Main effect of diagnosis was found on severity of compulsion, relative verbal IQ, executive function, verbal and visual memory, working memory and ALFF in precuneus, medial superior frontal gyrus, anterior cingulate and paracingulate gyri, and inferior parietal, postcentral gyrus, paracentral lobule. CONCLUSIONS: As a common feature in mental disorders, insight has its own special influence on neurocognition and possible structural/functional alterations in brain, and the influence is partly dependent of disease diagnosis.

Multiple sparganosis spinal infections mainly in the thoracic region: A case report.

BACKGROUND: Spinal infection with sparganosis is rarely seen, and multiple spinal infections with sparganosis in the thoracic spine have not been reported. CASE SUMMARY: In this case report, a 56-year old male patient suffered from back pain for 3 mo. Computed tomography examination of the thoracic spine showed bone destruction of the T4-5 vertebral body, as well as the right pedicle and lamina of T5. Magnetic resonance imaging showed high signals on T2W1 images and fat-suppressed images in the right vertebral body of T4-5 and the right pedicle and lamina of T5, a high signal in the vertebral canal, and similar high signals in the paravertebral and subcutaneous regions of the whole spine. Puncture biopsy showed sparganosis. Following definite diagnosis, the patient was treated with debridement of T4-5 infected lesions under a microscope, bone grafting and internal fixation. Postoperatively, the patient's back pain symptoms were significantly relieved; the incision healed after one-stage treatment, and albendazole antiparasitic treatment was administered. CONCLUSION: Puncture biopsy is the most reliable method to diagnose infection by sparganum. Removal of infected lesions under the microscope and albendazole for antiparasitic treatment are safe and effective.

[Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection].

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

Functional Characterization of the Ryanodine Receptor Gene in Diaphorina citri.

The Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae) is a major citrus pest spread around the world. It is also a vector of the bacterium 'Candidatus Liberibacter asiaticus', considered the cause of the fatal citrus disease huanglongbing (HLB). Insect ryanodine receptors (RyRs) are the primary target sites of diamide insecticides. In this study, full-length RyR cDNA from D. citri (named DcRyR) was isolated and identified. The 15,393 bp long open reading frame of DcRyR encoded a 5130 amino acid protein with a calculated molecular weight of 580,830 kDa. This protein had a high sequence identity (76-79%) with other insect homologs and a low sequence identity (43-46%) with mammals. An MIR domain, two RIH domains, three SPRY domains, four RyR repeat domains, an RIH-associated domain at the N-terminus, two consensus calcium-binding EF-hands, and six transmembrane domains were among the characteristics that DcRyR shared with insect and vertebrate RyRs. In expression analysis, the DcRyR gene displayed transcript abundance in all tissues and developmental stages as well as gene-differential and stage-specific patterns. In addition, diagnostic PCR experiments revealed that DcRyR had three potential alternative splice variants and that splicing events might have contributed to the various functions of DcRyR. However, diamide resistance-related amino acid residue mutations I4790M/K and G4946E were not found in DcRyR. These results can serve as the basis for further investigation into the target-based diamide pesticide resistance of D. citri.

Temporal characterization of biocycles of mycelium-bound composites made from bamboo and Pleurotus ostreatus for indoor usage.

Mycelium-bound composites (MBCs) are materials obtained by growing fungi on a ligno-cellulosic substrate which have various applications in packaging, furniture, and construction industries. MBCs are particularly interesting as they are sustainable materials that can integrate into a circular economy model. Indeed, they can be subsequently grown, used, degraded, and re-grown. Integrating in a meaningful biocycle for our society therefore demands that MBCs fulfil antagonistic qualities which are to be at the same time durable and biodegradable. In this study, we conduct experiments using MBCs made from the fungus species Pleurotus ostreatus grown on bamboo microfibers substrate. By measuring the variations of the mechanical properties with time, we provide an experimental demonstration of a biocycle for such composites for in-door applications. We found that the biocycle can be as short as 5 months and that the use of sustainable coatings is critical to increase the durability of the composites while maintaining biodegradability. Although there are many scenarios of biocycles possible, this study shows a tangible proof-of-concept example and paves the way for optimization of the duration of each phase in the biocycle depending on the intended application and resource availability.

[Plasma Levels and Clinical Significance of Cytokine Profile in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the levels of cytokines in the plasma of patients with multiple myeloma(MM), and explore its clinical significance. METHODS: The levels of 6 cytokines(IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) in the plasma of 59 newly diagnosed MM patients and 30 healthy controls were retrospectively analyzed, and the immunophenotypes were also analyzed. The plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were quantitatively detected by flow microsphere technology, and the differences of cytokines levels in each group were tested by Wilcoxon. RESULTS: The plasma concentration of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ in MM patients were all significantly higher than those in healthy controls (P<0.05). According to the ISS staging, there were no statistically significant difference in cytokines levels of patients at each stage (P>0.05). MM patients with high CD56 expression had higher plasma levels of IL-6 than the CD56 low expression group (41.74±62.73 vs 6.31±5.60 pg/ml) (P<0.05). The plasma level of IL-6 in MM patients with high CD117 expression was higher than that in the CD56 low expression group, but there was no statistically difference (P>0.05). The plasma level of IL-6 in MM patients was significantly decreased after chemotherapy (P<0.05). CONCLUSION: IL-6 is significantly increased in newly diagnosed MM patients, and is associated with the CD56 expression of abnormal plasma cells, which could provide important auxiliary effect on diagnosis of MM; at the same time, it is significantly decreased after chemotherapy, which may be suitable as a monitoring indicator in treatment of MM patients.

Development of a variant of dinutuximab with enhanced antitumor efficacy and reduced induction of neuropathic pain.

Dinutuximab (ch14.18) was the first approved monoclonal antibody against the tumor-associated antigen disialoganglioside GD2. Despite its success in treating neuroblastoma (NB), it triggers a significant amount of neuropathic pain in patients, possibly through complement-dependent cytotoxicity (CDC). We hypothesized that modifying ch14.18 using antibody engineering techniques, such as humanization, affinity maturation, and Fc engineering, may enable the development of next-generation GD2-specific antibodies with reduced neuropathic pain and enhanced antitumor activity. In this study we developed the H3-16 IgG1m4 antibody from ch14.18 IgG1. H3-16 IgG1m4 exhibited enhanced binding activity to GD2 molecules and GD2-positive cell lines as revealed by ELISA, and its cross-binding activity to other gangliosides was not altered. The CDC activity of H3-16 IgG1m4 was decreased, and the antibody-dependent cellular cytotoxicity (ADCC) activity was enhanced. The pain response after H3-16 IgG1m4 antibody administration was also reduced, as demonstrated using the von Frey test in Sprague-Dawley (SD) rats. In summary, H3-16 IgG1m4 may have potential as a monoclonal antibody with reduced side effects.

Relationships Between Multiple Dimensions of Insight and Neurocognition, Metacognition, and Social Cognition: A Meta-Analysis.

ABSTRACT: Insight is a complex and multidimensional concept, and has a complex relationship with cognition. A meta-analysis of 102 studies of 9396 patients was conducted to determine the magnitude of the relationship between insight and neurocognition, higher-order cognition in multiple mental disorders. Insight has been found moderately related to higher-order cognition, but only weakly related to neurocognition. The different relationship has been found between the dimensions of insight and higher-order cognition. Almost none of the correlational coefficients of insight and cognitive domains were found to differ significantly among the different diagnostic groups. In conclusion, insight may be essentially related to higher-order cognition, but not to neurocognition. The orientation and expression of different dimensions of insight might be different, and the relationship of insight and cognition might not be explained by specific diagnosis.