A New Strain of Metarhizium robertsii Isolated from Loess Plateau and Its Virulence and Pathological Characteristics against Monochamus alternatus.

Monochamus alternatus is a serious trunk-boring pest. The isolation and utilization of entomopathogenic fungi to manage M. alternatus is important. Here, a new strain GQH6 of Metarhizium robertsii, isolated from the Loess Plateau, was identified morphologically and molecularly. The virulence of the strain GQH6 against the third-instar larvae of M. alternatus was studied. Then, the pathological process, including symptom observation and histopathological observation, was also researched. The corrected mortality was 100% at 109 and 108 conidia/mL, and 88.89 ± 5.88% at 107 conidia/mL. The LC50 was 1.93 × 106 conidia/mL and the LC90 was 1.35 × 107 conidia/mL. And the LT50 of the strain GQH6 was 3.96 days at 109 conidia/mL, and 4.99 days at 108 conidia/mL. These virulence indices showed high virulence against M. alternatus larvae. In addition, the symptoms of the infected M. alternatus larvae were obvious. After one day, dark spots appeared and increased in number. By four days, white mycelia appeared. Finally, the larvae body became green. Similarly, the histopathological changes after infection were obvious, mainly manifested in muscle tissue rupture, adipose tissue fracture and midgut disintegration. These results demonstrated that the M. robertsii strain GQH6 isolated from the Loess Plateau was highly virulent against M. alternatus larvae of the third instar.

Corrigendum to "Aptamer-based cell-free detection system to detect target protein" [Synth Syst Biotechnol 6 (3) (2021) 209-215].

[This corrects the article DOI: 10.1016/j.synbio.2021.07.004.].

A small-scale, exploratory real-world study of nab-paclitaxel combined with oxaliplatin and tegafur in the perioperative treatment of advanced gastric cancer: a study protocol for a real-world clinical trial.

Background: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an optimized and improved derivative of paclitaxel with superior efficacy and fewer adverse reactions, and it is widely used in the treatment of advanced gastric cancer. However, there is a paucity of data regarding the safety and efficacy of nab-paclitaxel combined with oxaliplatin (LBP) and tegafur in the treatment of patients with advanced gastric cancer. Methods: This analysis is a prospective, single-center, open-label, historically controlled real-world study designed to include 10 patients with advanced gastric cancer treated with nab-paclitaxel combined with LBP and tegafur gimeracil oteracil potassium. The primary and main efficacy outcomes are safety indicators, including the incidence of adverse drug reactions and adverse events (AEs), as well as the outliers of laboratory indicators and vital signs. The secondary efficacy outcomes are overall survival (OS), objective response rate (ORR), disease control rate (DCR), and proportion of dose suspensions, dose reductions and discontinuations. Discussion: Based on the findings of previous studies, we wished to assess the safety and efficacy of nab-paclitaxel combined with LBP and tegafur in the treatment of advanced gastric cancer. The trial requires constant contact and monitoring. The purpose is to determine a superior protocol in terms of patient survival, and pathological and objective response. Trial Registration: This trial has been registered with the Clinical Trial Registry: NCT05052931 (registration date: 2021/9/12).

M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study.

Introduction: The efficacy and safety of immunotherapy have been widely recognized in gastrointestinal-related cancers. However, the efficacy of neoadjuvant camrelizumab for locally advanced esophageal squamous cell carcinoma (ESCC) has not been firmly established. This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response. Methods: We enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy. Results: A total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.

Light-Driven Synthetic Biology: Progress in Research and Industrialization of Cyanobacterial Cell Factory.

Light-driven synthetic biology refers to an autotrophic microorganisms-based research platform that remodels microbial metabolism through synthetic biology and directly converts light energy into bio-based chemicals. This technology can help achieve the goal of carbon neutrality while promoting green production. Cyanobacteria are photosynthetic microorganisms that use light and CO2 for growth and production. They thus possess unique advantages as "autotrophic cell factories". Various fuels and chemicals have been synthesized by cyanobacteria, indicating their important roles in research and industrial application. This review summarized the progresses and remaining challenges in light-driven cyanobacterial cell factory. The choice of chassis cells, strategies used in metabolic engineering, and the methods for high-value CO2 utilization will be discussed.

Landscape of RB1 alterations in 22,432 Chinese solid tumor patients.

Background: The human retinoblastoma susceptibility gene (RB1) is a tumor-suppressor gene mutated at different frequencies in many different cancers. The aim of the present study was to investigate the distribution of overall RB1 mutation and different mutation types in a range of Chinese patients with solid tumors. Methods: We investigated RB1 mutations in formalin-fixed, paraffin-embedded (FFPE) tissues of cancer patients who underwent next-generation sequencing (NGS) at 3DMed Clinical Laboratory Inc from January 1, 2017 to April 15, 2020. Results: Genomic alterations in RB1 were identified in 1,712 (7.6%) of 22,432 patients with more than 20 different cancer entities (58% males and 42% females, median age: 60 years). RB1 mutations occurred most frequently in small-cell lung cancer (SCLC; 138/165, 83.6%), followed by neuroendocrine neoplasms (40/170, 23.5%), bladder cancer (40/209, 19.1%), hepatocellular carcinoma (233/1,649, 14.1%), sarcomas (71/554, 12.8%), and esophageal cancer (32/293, 10.9%). Of these 1,712 patients, 185 (10.8%) had germline RB1 mutations. When stratified by mutational type, 1,258 (5.6%) had single-nucleotide variants (SNVs), 59 (0.3%) had fusions, and 210 (0.9%) had RB1 loss. Conclusions: Our findings indicate that RB1 alterations are widely distributed in solid cancers of many different histotypes in China, with specific mutations differing largely among different tumor types. The present study provides a comprehensive landscape of RB1 mutations in Chinese solid tumor patient and suggests a novel therapeutic target for cancer treatment.

Gut microbiota imbalance mediates intestinal barrier damage in high-altitude exposed mice.

The environmental conditions in high-altitude areas can induce gastrointestinal disorders and changes in gut microbiota. The gut microbiota is closely related to a variety of gastrointestinal diseases, although the underlying pathogenic mechanisms are not well-identified. The present study aimed to investigate the regulatory effect of high altitude on intestinal dysfunction via gut microbiota disturbance. Forty C57BL/6J mice were divided into four groups: one plain control group (CON) and three high-altitude exposure groups (HAE) (altitude: 4000 m a.s.l.; oxygen content: 12.7%; 1-, 2- and 4-week exposure). Another set of 40 mice was divided into two CON and two HAE subgroups. Antibiotic cocktails were administered to one CON and HAE groups and autoclaved water was administered to the second CON and HAE groups for 4 weeks, respectively. In the fecal microbiota transplantation experiment, there were four transplantation groups, which received, respectively: phosphate-buffered saline for 2 weeks, feces from CON for 2 weeks, feces from HAE-4W for 2 weeks, and HAE-4W for 4 weeks. Hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and a quantitative reverse transcriptase-polymerase chain reaction were applied to detect changes in intestinal cellular structure, morphology, apoptosis and intestinal inflammatory response. Fecal microbiota was analyzed using 16S rDNA amplicon sequencing. A high-altitude environment changed the ecological balance of gut microbiota in mice and caused damage to the intestinal structure and mucosal barrier. Interestingly, similar damage, which was inhibited by antibiotic cocktails at high altitude, was observed in mice transplanted with fecal microbiota from HAE. A high-altitude environment contributes to dyshomeostasis of gut microbiota, thereby impairing the intestinal mucosal barrier, eventually inducing and exacerbating intestinal damage.

Aptamer-based cell-free detection system to detect target protein.

Biomarkers of disease, especially protein, show great potential for diagnosis and prognosis. For detecting a certain protein, a binding assay implementing antibodies is commonly performed. However, antibodies are not thermally stable and may cause false-positive when the sample composition is complicated. In recent years, a functional nucleic acid named aptamer has been used in many biochemical analysis cases, which is commonly selected from random sequence libraries by using the systematic evolution of ligands by exponential enrichment (SELEX) techniques. Compared to antibodies, the aptamer is more thermal stable, easier to be modified, conjugated, and amplified. Herein, an Aptamer-Based Cell-free Detection (ABCD) system was proposed to detect target protein, using epithelial cell adhesion molecule (EpCAM) as an example. We combined the robustness of aptamer in binding specificity with the signal amplification ability of CRISPR-Cas12a's trans-cleavage activity in the ABCD system. We also demonstrated that the ABCD system could work well to detect target protein in a relatively low limit of detection (50-100 nM), which lay a foundation for the development of portable detection devices. This work highlights the superiority of the ABCD system in detecting target protein with low abundance and offers new enlightenment for future design and development.

Idiopathic fibrous mediastinitis with refractory pleural effusion: a case report and literature review.

Fibrous mediastinitis is a rare progressive disease characterized by invasive proliferation of fibrous tissue in the mediastinum. This tissue proliferation leads to compression of the mediastinal structures in the thoracic cavity, including the pulmonary vessels, esophagus, and trachea, causing corresponding symptoms and complications such as pulmonary hypertension. In clinical practice, the diagnosis of fibrous mediastinitis is often delayed or missed because of the rarity and variable clinical manifestations of this condition. This article presents a case of idiopathic fibrous mediastinitis that manifested as pleural effusion of unknown etiology along with a review of the relevant literature.

Differential diagnosis for suspected cases of coronavirus disease 2019: a retrospective study.

BACKGROUND: Since December 2019, the coronavirus disease 2019 (COVID-19) has infected more than 12,322,000 people and killed over 556,000 people worldwide. However, Differential diagnosis remains difficult for suspected cases of COVID-19 and need to be improved to reduce misdiagnosis. METHODS: Sixty-eight cases of suspected COVID-19 treated in Wenzhou Central Hospital from January 21 to February 20, 2020 were divided into confirmed and COVID-19-negative groups based on the results of real-time reverse transcriptase polymerase chain reaction (RT-PCR) nucleic acid testing of the novel coronavirus in throat swab specimens to compare the clinical symptoms and laboratory and imaging results between the groups. RESULTS: Among suspected patients, 17 were confirmed to COVID-19-positive group and 51 were distinguished to COVID-19-negative group. Patients with reduced white blood cell (WBC) count were more common in the COVID-19-positive group than in the COVID-19-negative group (29.4% vs 3.9%, P = 0.003). Subsequently, correlation analysis indicated that there was a significant inverse correlation existed between WBC count and temperature in the COVID-19-positive patients (r = - 0.587, P = 0.003), instead of the COVID-19-negative group. But reduced lymphocyte count was no different between the two groups (47.1% vs 25.5%, P = 0.096). More common chest imaging characteristics of the confirmed COVID-19 cases by high-resolution computed tomography (HRCT) included ground-glass opacities (GGOs), multiple patchy shadows, and consolidation with bilateral involvement than COVID-19-negative group (82.4% vs 31.4%, P = 0.0002; 41.2% vs 17.6% vs P = 0.048; 76.5% vs 43.1%, P = 0.017; respectively). The rate of clustered infection was higher in COVID-19-positive group than COVID-19-negative group (64.7% vs 7.8%, P = 0.001). Through multiplex PCR nucleic acid testing, 2 cases of influenza A, 3 cases of influenza B, 2 cases of adenovirus, 2 cases of Chlamydia pneumonia, and 7 cases of Mycoplasma pneumoniae were diagnosed in the COVID-19-negative group. CONCLUSIONS: WBC count inversely correlated with the severity of fever, GGOs, multiple patchy shadows, and consolidation in chest HRCT and clustered infection are common but not specific features in the confirmed COVID-19 group. Multiplex PCR nucleic acid testing helped differential diagnosis for suspected COVID-19 cases.

Postoperative intraperitoneal hyperthermic perfusion improve survival for advanced gastric cancer.

To evaluate the value of intraperitoneal hyperthermic perfusion (IPHP) in the treatment of gastric cancer.Gastric cancer (GC) is a malignancy with poor prognosis, recent years have demonstrated advances in the use of IPHP for the treatment of advanced gastric cancer (AGC), but the outcome is controversial.Between January 2015 and January 2017, 134 patients with GC were treated with IPHP in our surgery department, 130 of them were advanced GC patients, and other 1439 cases were treated without IPHP for comparison. In this retrospective cohort study, demographic, perioperative data, and follow-up data were analyzed by univariant analysis, Kaplan-Meier and Cox regression survival analysis.We found the 1-year survival in IPHP group was significantly longer than it in non-IPHP group (85.5% vs 73.8%, P = .027). and IPHP decreased mortality 1.8 times in 2-year course (OR = 0.556, P = .004). The incidence rate of total complications in IPHP group was similar to that in the Non-IPHP group (6.67% vs 7.46%, respectively; P = .718). We classified all patients into four groups, operation alone, operation + chemotherapy, operation + IPHP, and operation + IPHP + chemotherapy. The 1-year survival in the groups was 70.2%, 77.5%, 83.1%, and 93.5%, respectively (P = .001), compared with the group of operation alone, the 2-year mortality risk was decreased 1.76 times (OR = 0.569, P = .030) and 2.59 times (OR = 0.385, P = .022) in operation + IPHP group and operation + IPHP + chemotherapy group.Our results suggest that IPHP could contribute to improve survival of patients with gastric cancer. And the modality of operation + IPHP + chemotherapy is the optimal treatment modality for gastric cancer.

Is the signet ring cell histological type a positive prognostic factor for gastric adenocarcinoma after D2 radical gastrectomy?

BACKGROUND: Previous studies indicated the histological type might have prognostic value in gastric adenocarcinoma patients. The aim of this study was to clarify whether the signet ring cell (SRC) histological type of gastric adenocarcinoma is associated with worse prognosis than pure gastric adenocarcinoma without any mixed histological component (PGA) for patients underwent D2 radical gastrectomy. METHOD: By the database of 6205 surgical patients with gastric adenocarcinoma at our department between September 2008 and May 2015, we investigated 133 SRC patients and 2847 PGA patients who underwent D2 radical gastrectomy. The clinic and pathologic data, especially tumor and pathology molecular markers, and 5-year overall survival rate were compared between SRC and PGA. The univariate and multivariate analysis were used to testify the prognosis significance of SRC. RESULTS: SRC was more frequently found in younger (<50), female patients, lower part of stomach and easy to metastasize lymph nodes. And more positive CA19-9 and less positive EGFR were obtained in SRC. The 5-year survival rate was not different between SRC and PGA after D2 radical gastrectomy, even assessed by T stage. Multivariate analysis showed age, T and N stage, CEA, CA19-9 and CA125 were the independent prognostic factors, not included the SRC histological type. CONCLUSION: Although SRC histological type of gastric adenocarcinoma after D2 radical gastrectomy had its own clinic-pathologic characters, especially in molecular tumor and pathological markers, the histological type of SRC was a negative prognostic factor in gastric adenocarcinoma patients after D2 radical gastrectomy.

Isolation and characterization of eleven polymorphic microsatellite loci for the valuable medicinal plant Dendrobium huoshanense and cross-species amplification.

Dendrobium huoshanense (Orchidaceae) is a perennial herb and a widely used medicinal plant in Traditional Chinese medicine (TCM) endemic to Huoshan County town in Anhui province in Southeast China. A microsatellite-enriched genomic DNA library of D. huoshanense was developed and screened to identify marker loci. Eleven polymorphic loci were isolated and analyzed by screening 25 individuals collected from a natural population. The number of alleles per locus ranged from 2 to 5. The observed and expected heterozygosities ranged from 0.227 to 0.818 and from 0.317 to 0.757, respectively. Two loci showed significant deviations from Hardy-Weinberg equilibrium and four of the pairwise comparisons of loci revealed linkage disequilibrium (p < 0.05). These microsatellite loci were cross-amplified for five congeneric species and seven loci can be amplified in all species. These simple sequence repeats (SSR) markers are useful in genetic studies of D. huoshanense and other related species and in conservation decision-making.

[Isolation and analysis of polymorphic microsatellite loci in Dendrobium huoshanense].

OBJECTIVE: To investigate the genetic diversity and structure of Dendrobium huoshanense, a (CT)n enriched microsatellite library was constructed using a magnetic beads enrichment procedure. METHOD: The 3'-biotinylated oligonucleotide probe was used to hybridize with the digested D. huoshanense genomic DNA fragments whose both ends were ligated with adaptors. The hybridized complex was then combined with the streptavidin-coated magnetic beads. The captured microsatellite fragments were eluted, collected and cloned into pMD19-T vector. The recombinant plasmids were transformed into Escherichia coli DH5alpha competent cells. The clones that yielded two or more bands contained microsatellite fractions. Positive clones were screened and sequenced. Thirty pairs of primers were designed and synthesized. Polymorphism at each locus was determined using 24 individuals from a natural population from Huoshan county town in Anhui province. RESULT: Twelve polymorphic microsatellite loci from the microsatellite-enriched genomic library were newly developed across 24 D. huoshanense individuals. In total, 65 alleles were identified, and the number of alleles per locus ranged from 2 to 8. The mean observed and expected heterozygosities were 0.500 and 0.638, respectively. Two loci significantly deviated from Hardy-Weinberg equilibrium (P<0.05), which could be due to the presence of null alleles. Furthermore, three of twelve loci showed significant linkage disequilibrium (P<0.05). CONCLUSION: These results suggest that the identified polymorphic microsatellite markers will be useful in population genetic studies of D. huoshanense.

[Application of ThinPrep cytology test in the diagnosis of lung cancer].

OBJECTIVE: To explore the diagnostic value of ThinPrep cytology test (TCT) in lung cancer. METHODS: 353 cases of bronchoalveolar lavage fluid (BALF) and(or) bronchial brushing cytology (192 cases from lung cancer patients and 161 cases from benign lung disease patients) were detected with TCT and method of direct smear, respectively. The sensitivity and specificity of two methods was compared. RESULTS: The sensitivity and specificity of TCT were 39.6% and 99.4%. And which of direct smear method were 8.3% and 100%, respectively. The sensitivity of TCT was significantly higher than that of method of direct smear in the diagnosis of lung cancer (P < 0.01). There were 71 patients who underwent BALF and bronchial brushing cytology simultaneously, the sensitivity of TCT of BALF was higher than that of bronchial brushing cytology (P < 0.05). Of the 69 cases which had both TCT and histopathological results, TCT and pathology concordance rate was 84.1%. CONCLUSION: TCT has more diagnostic value in lung cancer; BALF is more preponderant than bronchial brushing cytology by TCT in the diagnosis of lung cancer.