Single-cell atlas profiling revealed cellular characteristics and dynamic changes after PD-1 blockade therapy of brain metastases from laryngeal squamous cell carcinoma.

Brain metastasis (BM) in laryngeal squamous cell carcinoma (LSCC) is uncommon but prognosis is poor. Anti-PD-1 immunotherapy benefits some advanced LSCC cases, yet its efficiency is limited by tumor complexity. We analyzed paired metastatic tumor samples from before and after immunotherapy using single-cell RNA sequencing (scRNA-seq), along with a primary LSCC dataset and bulk RNA sequencing. This identified changes post-immunotherapy and revealed differences in single-cell transcriptomes among LSCC, primBM, and neoBM. Our findings show that anti-PD-1 treatment suppresses metastasis-promoting pathways like VEGF and EMT in cancer cells, and alters immune cell functions. Notably, it upregulates T cell activation, leading to CD8 T cell exhaustion from excess heat shock proteins, notably HSPA8. However, CD8 T cell cytotoxic functions improve post-treatment. In myeloid cells, anti-PD-1 therapy enhances antigen presentation and promotes a proinflammatory shift post-metastasis. Additionally, NUPR1 is linked to BM in LSCC, and NEAT1 is a potential metastatic cancer cell cycle participant. Our study provides insights into cancer heterogeneity and the impact of PD-1 immunotherapy on metastasis, aiding precise diagnosis and prognosis.

Doxycycline and minocycline in Helicobacter pylori treatment: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The decreasing Helicobacter pylori eradication rate and the increasing antibiotic resistance trend are of great concern. Therefore, new and effective therapies are needed for H. pylori infection. We conducted a systematic review and meta-analysis to assess the efficacy and safety of semisynthetic tetracycline regimens in H. pylori treatment. METHODS: PubMed, EMBASE, and the Cochrane library were searched. The outcome indicators were the eradication rate, risk ratio (RR, ie, the risk of the semisynthetic tetracycline regimen relative to the control), and 95% confidence interval (95% CI). Controls were patients undergoing any other treatment without semisynthetic tetracycline. RESULTS: Twenty-three studies with 5240 participants were included. The eradication rates of triple regimens with semisynthetic tetracyclines in most studies were less than 70% in both the intention-to-treat (ITT) and the per-protocol (PP) analyses. The pooled eradication rates of quadruple therapies with doxycycline and controls were 95% and 84% in the PP analyses, respectively. The pooled RR associated with efficacy in the quadruple therapy with doxycycline group compared with the control group was 1.12 (95% CI: 1.04-1.20) in the PP analysis. The pooled RR of side effects in the quadruple therapy with doxycycline group compared with the control group was 1.01 (95% CI: 0.65-1.55). CONCLUSION: Seven-day and ten-day quadruple therapy with doxycycline might be an optional first-line therapy. The safety of regimens containing semisynthetic tetracyclines was relatively satisfactory. However, the triple regimen is not recommended.

Desulfurization with Thialkalivibrio versutus immobilized on magnetic nanoparticles modified with 3-aminopropyltriethoxysilane.

OBJECTIVE: Thialkalivibrio versutus D301 cells were immobilized on Fe3O4 nanoparticles (NPs) synthesized by an improved chemical coprecipitation method and modified with 3-aminopropyltriethoxysilane (APTES), then the immobilized cells were used in sulfur oxidation. RESULTS: The prepared Fe3O4-APTES NPs had a narrow size distribution (10 ± 2 nm) and were superparamagnetic, with a saturation magnetization of 60.69 emu/g. Immobilized cells had a saturation magnetization of 34.95 emu/g and retained superparamagnetism. The optimum conditions for cell immobilization were obtained at pH 9.5 and 1 M Na+. The immobilization capacity of Fe3O4-APTES NPs was 7.15 g DCW/g-NPs that was 2.3-fold higher than that of Fe3O4 NPs. The desulfurization efficiency of the immobilized cells was close to 100%, having the same sulfur oxidation capacity as free cells. Further, the immobilized cells could be reused at least eight times, retaining more than 85% of their desulfurization efficiency. CONCLUSION: Immobilization of cells with the modified magnetic NPs efficiently increased cell controllability, have no effect on their desulfurization activity and could be effectively used in large-scale industrial applications.

Improvement of desulfurizing activity of haloalkaliphilic Thialkalivibrio versutus SOB306 with the expression of Vitreoscilla hemoglobin gene.

OBJECTIVE: To construct efficient transformation and expression system and further improve desulfurizing activity of cells through expression of Vitreoscilla hemoglobin (VHb) in haloalkaliphilic Thialkalivibrio versutus SOB306. RESULTS: We transferred plasmids pKT230 and pBBR-smr into T. versutus SOB306 via a conjugation method. We identified four promoters from among several predicted promoters by scoring for streptomycin resistance, and finally selected tac and p3 based on the efficiency of expression of red fluorescent protein (RFP). Expression of RFP when regulated by tac was more than three times that of p3 in SOB306. Further, we expressed VHb under the control of tac promoter in SOB306. Expression of VHb was verified using CO-difference spectra. The results showed that VHb expression can boost sulfur metabolism, as evidenced by an increase of about 11.7 ± 1.8% in the average rate of thiosulfate removal in the presence of VHb. CONCLUSION: A conjugation transfer and an expression system for Thialkalivibrio, has been developed for the first time and used for expression of VHb to improve desulfurizing activity.

PfAgo-Based Zika Virus Detection.

As a mosquito-borne flavivirus, Zika virus (ZIKV) has been identified as a global health threat. The virus has been linked to severe congenital disabilities, including microcephaly and other congenital malformations, resulting in fatal intrauterine death. Therefore, developing sensitive and specific methods for the early detection and accurate diagnosis of the ZIKV is essential for controlling its spread and mitigating its impact on public health. Herein, we set up a novel nucleic acid detection system based on Pyrococcus furiosus Argonaute (PfAgo)-mediated nucleic acid detection, targeting the non-structural protein 5 (NS5) region of the ZIKV genome (abbreviated ZIKV-PAND). Without preamplification with the polymerase chain reaction (PCR), the minimum detection concentration (MDC) of ZIKV-PAND was about 10 nM. When introducing an amplification step, the MDC can be dramatically decreased to the aM level (8.3 aM), which is comparable to qRT-PCR assay (1.6 aM). In addition, the diagnostic findings from the analysis of simulated clinical samples or Zika virus samples using ZIKV-PAND show a complete agreement of 100% with qRT-PCR assays. This correlation can aid in the implementation of molecular testing for clinical diagnoses and the investigation of ZIKV infection on an epidemiological scale.

Self-cultivating anammox granules for enhancing wastewater nitrogen removal in nitrification-denitrification flocculent sludge system.

The feasibility of self-cultivating anammox granules for enhancing wastewater nitrogen removal was investigated in a nitrification-denitrification flocculent sludge system. Desirable nitrogen removal efficiency of 84 ± 4 % was obtained for the influent carbon to nitrogen ratio of 1-1.3 (NH4+-N: 150-200 mg N/L) via alternate anaerobic/oxic/anoxic mode. Meanwhile, some red granular sludge was formed in the system. The abundance and activity of anaerobic ammonia oxidation bacteria (AnAOB) increased from 'not detected' in seed sludge to 0.57 % and 29.4 ± 0.7 mg N/(g mixed liquor volatile suspended solids·h) in granules, respectively, suggesting successful cultivation of anammox granules. Furthermore, some denitrifying bacteria with capability of partial denitrification were enriched, such as Candidatus Competibacter (2.45 %) and Thauera (5.75 %), which could cooperate with AnAOB, facilitating AnAOB enrichment. Anammox was dominant in nitrogen removal with the contribution to nitrogen removed above 68.8 ± 0.3 %. The strategy of self-cultivating anammox granules could promote the application of anammox.

Investigating causal associations among gut microbiota, metabolites, and psoriatic arthritis: a Mendelian randomization study.

Background: Currently, there has been observed a significant alteration in the composition of the gut microbiome (GM) and serum metabolites in patients with psoriatic arthritis (PsA) compared to healthy individuals. However, previous observational studies have shown inconsistent results regarding the alteration of gut microbiota/metabolites. In order to shed light on this matter, we utilized Mendelian randomization to determine the causal effect of GM/metabolites on PsA. Methods: We retrieved summary-level data of GM taxa/metabolites and PsA from publicly available GWAS statistics. Causal relationships between GM/metabolites and PsA were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the robustness of our findings, we conducted sensitivity analyses, multivariable MR analysis (MVMR), and additional analysis including replication verification analysis, LDSC regression, and Steiger test analysis. Furthermore, we investigated reverse causality through a reverse MR analysis. Finally, we conducted an analysis of expression quantitative trait loci (eQTLs) involved in the metabolic pathway to explore potential molecular mechanisms of metabolism. Results: Our findings reveal that eight GM taxa and twenty-three serum metabolites are causally related to PsA (P < 0.05). Notably, a higher relative abundance of Family Rikenellaceae (ORIVW: 0.622, 95% CI: 0.438-0.883, FDR = 0.045) and elevated serum levels of X-11538 (ORIVW: 0.442, 95% CI: 0.250-0.781, FDR = 0.046) maintain significant causal associations with a reduced risk of PsA, even after adjusting for multiple testing correction and conducting MVMR analysis. These findings suggest that Family Rikenellaceae and X-11538 may have protective effects against PsA. Our sensitivity analysis and additional analysis revealed no significant horizontal pleiotropy, reverse causality, or heterogeneity. The functional enrichment analysis revealed that the eQTLs examined were primarily associated with glycerolipid metabolism and the expression of key metabolic factors influenced by bacterial infections (Vibrio cholerae and Helicobacter pylori) as well as the mTOR signaling pathway. Conclusion: In conclusion, our study demonstrates that Family Rikenellaceae and X-11538 exhibit a strong and negative causal relationship with PsA. These particular GM taxa and metabolites have the potential to serve as innovative biomarkers, offering valuable insights into the treatment and prevention of PsA. Moreover, bacterial infections and mTOR-mediated activation of metabolic factors may play an important role in this process.

Efficacy and safety of indocyanine green tracer-guided lymph node dissection in minimally invasive radical gastrectomy for gastric cancer: A systematic review and meta-analysis.

Background: The implementation of indocyanine green (ICG) tracer-guided lymph node dissection is still in the preliminary stages of laparoscopic surgery, and its safety and efficacy for gastric cancer remain unclear. Methods: A systematic review was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and Scopus to identify relevant subjects from inception to June 2022. The core indicators were the total number of harvested lymph nodes and the safety of the laparoscopic gastrectomy with ICG. A meta-analysis was performed to estimate the pooled weighted mean difference (WMD) and 95% confidence interval (CI). Results: Thirteen studies and 2,027 participants were included (642 for the ICG-group and 1,385 for the non-ICG group). The mean number of lymph nodes dissected in the ICG group was significantly greater than that in the non-ICG group (WMD = 6.24, 95% CI: 4.26 to 8.22, P <0.001). However, there was no significant difference in the mean number of positive lymph nodes dissected between the ICG and the non-ICG groups (WMD = 0.18, 95% CI: -0.70 to 1.07, P = 0.879). Additionally, ICG gastrectomy did not increase the risk in terms of the operative time, estimated blood loss, and postoperative complications. Conclusion: ICG tracer with favorable safety increases the number of harvested lymph nodes but not the number of positive lymph nodes in laparoscopic gastrectomy. More high-quality, large-sample-size randomized controlled trials are still needed to enhance this evidence.

The complete chloroplast genome of Kolkwitzia amabilis (Caprifoliaceae), an endangered horticultural plant in China.

The complete chloroplast genome of Kolkwitzia amabilis (Caprifoliaceae) is first presented in the current study. The cp genome of K. amabilis was 156 875 bp in length and composed of two short inverted repeat (IRa and IRb) regions of 23 946 bp which were separated by a small single copy (SSC) region of 18 846 bp and a large single copy (LSC) region of 90 137 bp. The genome encoded 130 genes contained 81 coding genes, 39 tRNA genes, and 8 rRNA genes. The overall AT content of K. amabilis is 61.6% and the corresponding values of the SSC, LSC and IR regions are 66.8%, 64.1%, and 57.3%, respectively. The phylogenetic analysis based on the maximum parsimony tree revealed that K. amabilis was closely related to Lonicera japonica.

The complete chloroplast genome of Dipteronia sinensis (Aceraceae), an endangered endemic species to China.

The complete chloroplast sequence of D. sinensis was reported in this study. The total length was 157 080 bp containing a pair of 26 766 bp inverted repeat regions (IRa and IRb), which were separated by a small single copy regions and a large single copy regions (SSC and LSC) of 18 093 and 85 455 bp, respectively. A total of 138 functional genes were annotated, which included 90 protein-coding genes, 40 tRNAs, and eight rRNA genes. The overall GC content of the complete chloroplast genome is 37.8% and in LSC, SSC and IR regions were 35.9%, 32.1%, and 42.7%, respectively. The maximum likelihood (ML) phylogenetic analysis revealed that D. sinensis was closely related to A. buergerianum subsp. Ningpoense in Sapindales order.

Effective degradation of rhodamine B by electro-Fenton process, using ferromagnetic nanoparticles loaded on modified graphite felt electrode as reusable catalyst: in neutral pH condition and without external aeration.

Polytetrafluoroethylene/ferromagnetic nanoparticle/carbon black (PTFE/MNP/CB)-modified graphite felt (GF) was successfully applied as cathode for the mineralization of rhodamine B (RhB) in electro-Fenton (EF) process. The modified cathode showed high decolorization efficiency for RhB solution even in neutral pH condition and without external aeration, achieving nearly complete decolorization and 89.52 % total organic carbon (TOC) removal after 270-min oxidation with the MNP load 1.2 g at 50 A/m(2). Moreover, the operational parameters (current density, MNP load, initial pH, and airflow rate) were optimized. After that, adsorption isotherm was also conducted to compare the absorption quantity of CB and carbon nanotube (CNT). Then, the surface morphologies of MNPs were characterized by transmission electron microscope (TEM), energy-dispersive X-ray detector (EDX), and Fourier transform infrared spectroscopy (FTIR); and the modified cathode was characterized by SEM and contact angle. Finally, the stability and reusability of modified cathode were tested. Result uncovered that the PTFE/MNP/CB-modified cathode has the potential for industrial application and the solution after treatment was easily biodegradable.

Mass Spectrometric Analysis of N-Glycoforms of Soybean Allergenic Glycoproteins Separated by SDS-PAGE.

Glycosylation of many proteins has been revealed to be closely related with food allergies, and screening and structural analysis of related glycoproteins and glycoallergens are essential for studies in this field. Herein, we describe detailed N-glycoform analysis of all glycoprotein fractions of soybean protein isolate (SPI) separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to disclose structural features of the glycan moieties of more soybean glycoproteins. SPI was fractionated by SDS-PAGE, and the generated protein bands were recovered and subjected to in-gel N-glycan release and labeling using a one-pot method newly developed by our group, followed by detailed analysis by electrospray ionization mass spectrometry (ESI-MS) and online hydrophilic interaction liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS). As a result, we found seven bands mainly containing oligomannose-type glycans; two mainly contain core α1,3-fucosylated glycans, and six have no glycans. This study is the first report that discovers core α1,3-fucosylated N-glycans in bands 1, 2, and 6 and discloses bands 3, 4, 5, and 7 as glycoproteins and their N-glycoforms. Therefore, it can expand our knowledge about soybean protein glycosylation and provide significant structural reference for research of soybean allergens.