Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study.

Introduction: Global phase III clinical trials have shown superior hypoglycemic efficacy to insulin and other oral hypoglycemic agents. However, there is a scarcity of real-world data comparing different glucagon-like peptide 1 receptor agonist (GLP-1RA) directly. This study aimed to assess the safety and effectiveness of various GLP-1RA in treating type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify predictive factors for favorable treatment outcomes. Methods: This was a retrospective, single-center, real-world study. The changes in HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the percentage of participants who achieved HbA1c of <7%, 7%-8%, and ≥ 8% after GLP-1RA treatment was analyzed. The clinical factors that affect the effectiveness of GLP-1RA were analyzed. Results: At baseline, the 249 participants had a mean baseline HbA1c of 8.7 ± 1.1%. After at least three months of follow-up, the change in HbA1c was -0.89 ± 1.3% from baseline. Dulaglutide exerted a more significant hypoglycemic effect than immediate-release exenatide. The percentage of participants who achieved HbA1c<7% was substantial, from 6.0% at baseline to 28.9%. Average body weight decreased by 2.02 ± 3.8 kg compared to baseline. After GLP-1RA treatment, the reduction in SBP was 2.4 ± 7.1 mmHg from baseline. A shorter duration of diabetes and a higher baseline HbA1c level were more likely to achieve a good response in blood glucose reduction. Conclusions: This study provided real-world evidence showing that GLP-1RA significantly improved HbA1c, body weight, and SBP. The results can inform the decision-making about GLP-1RA treatment in daily clinical practice.

RPL35A promotes the progression of cholangiocarcinoma by mediating HSPA8 ubiquitination.

BACKGROUND: Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. METHODS: The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. RESULTS: RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. CONCLUSION: RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Application of dose-gradient function in reducing radiation induced lung injury in breast cancer radiotherapy.

OBJECTIVE: Try to create a dose gradient function (DGF) and test its effectiveness in reducing radiation induced lung injury in breast cancer radiotherapy. MATERIALS AND METHODS: Radiotherapy plans of 30 patients after breast-conserving surgery were included in the study. The dose gradient function was defined as DGH=VDVp3, then the area under the DGF curve of each plan was calculated in rectangular coordinate system, and the minimum area was used as the trigger factor, and other plans were triggered to optimize for area reduction. The dosimetric parameters of target area and organs at risk in 30 cases before and after re-optimization were compared. RESULTS: On the premise of ensuring that the target dose met the clinical requirements, the trigger factor obtained based on DGF could further reduce the V5, V10, V20, V30 and mean lung dose (MLD) of the ipsilateral lung in breast cancer radiotherapy, P < 0.01. And the D2cc and mean heart dose (MHD) of the heart were also reduced, P < 0.01. Besides, the NTCPs of the ipsilateral lung and the heart were also reduced, P < 0.01. CONCLUSION: The trigger factor obtained based on DGF is efficient in reducing radiation induced lung injury in breast cancer radiotherapy.

High-expressed ACAT2 predicted the poor prognosis of platinum-resistant epithelial ovarian cancer.

BACKGROUND: Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC). METHODS: ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models. RESULTS: ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15-4.11, P = 0.017) affected OS independently, rather than PFI and PFS. CONCLUSION: The expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.

Integrin αvß1 facilitates ACE2-mediated entry of SARS-CoV-2.

Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins facilitate the ACE2-mediated cellular entry of SARS-CoV-2. We first tested the susceptibility of a panel of human cell lines to SARS-CoV-2 infection using the spike protein pseudotyped virus assay and examined the expression levels of integrins in these cell lines by qPCR, western blot and flow cytometry. We found that integrin αvß1 was highly enriched in the SARS-CoV-2 susceptible cell lines. Additional studies demonstrated that RGD (403-405)→AAA mutant was defective in binding to integrin αvß1 compared to its wild type counterpart, and anti-αvß1 integrin antibodies significantly inhibited the entry of SARS-CoV-2 into the cells. Further studies using mouse NIH3T3 cells expressing human ACE2, integrin αv, integrin ß1, and/or integrin αvß1 suggest that integrin αvß1 was unable to function as an independent receptor but could significantly facilitate the cellular entry of SASR-CoV-2. Finally, we observed that the Omicron exhibited a significant increase in the ACE2-mediated viral entry. Our findings may enhance our understanding of the pathogenesis of SARS-CoV-2 infection and offer potential therapeutic target for COVID-19.

Application research on reducing radiation-induced lung injury with a trigger operator based on overlap volume histogram (OVH) in breast cancer postoperative radiotherapy.

This study aims to develop a trigger operator based on the Overlap Volume Histogram (OVH) and examined its effectiveness in enhancing plan quality to minimize radiation-induced lung injury in postoperative radiotherapy for breast cancer. This trigger operator was applied for plan re-optimization to the previous Volumetric Modulated Arc Therapy (VMAT) plans of 16 left breast conserving surgery cases. These cases were categorized into a Contiguous Group (CG) and a Separated Group (SG) based on the relative position between the target and the Left-Lung (L-Lung). We investigated the changes in Vx, mean dose, and Normal Tissue Complication Probability (NTCP) values of organs-at-risk (OARs) before and after using the trigger operator. The Pairwise Sample T test was employed to evaluate the differences in indices between the two groups before and after optimizations. The trigger operator effectively initiated plan re-optimization. The values of V5, V10, V20, V30, and V40 of the L-Lung, as well as the mean dose of the heart, all decreased after re-optimization. The Pairwise Sample T test results showed statistically significant differences in the V20, V30, and V40 of the L-Lung in the CG (P < 0.01), and in the V5, V10, V20, V30, and V40 of the L-Lung in the SG (P < 0.01). Our findings suggest that the proposed trigger operator can improve plan quality, thereby reducing radiation-induced lung injury in postoperative radiotherapy for breast cancer.

Effect of a Bacterial Laccase on the Quality and Micro-Structure of Whole Wheat Bread.

The gluten protein content in whole-wheat flour is low, which affects the elasticity and viscosity of the dough. Enzymatic modification of the protein may result in a network that mimics gluten, which plays an important role in the processing of whole-wheat foods. In this study, the effects of Halomonas alkaliantartica laccase (LacHa) on the quality parameters of whole-wheat bread were investigated. The optimum dosage of LacHa was 4 U/100 g of whole-wheat flour. At this dosage, whole-wheat bread exhibited the best specific volume and optimum texture parameters. Laccase also extended the storage duration of whole-wheat bread. We analyzed the micro-structure of the dough to determine its gluten-free protein extractable rate and free sulfhydryl group content, and verify that LacHa mediates cross-linking of gluten-free proteins. The results demonstrated that the cross-linking of gluten-free protein by LacHa improves the texture of whole-wheat bread. As a flour improver, LacHa has great developmental and application potential in baked-food production.

Lipid alternations in the plasma of COVID-19 patients with various clinical presentations.

Background: COVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive. Methods: This study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups. Results: We found 175 differentially expressed lipids associated with SASR-CoV-2 infection, disease severity, and viral persistence in patients with COVID-19. PC (O-20:1/20:1), PC (O-20:1/20:0), and PC (O-18:0/18:1) better distinguished asymptomatic infected individuals from normal individuals. Furthermore, some patients tested positive for SARS-CoV-2 nucleic acid by RT-PCR but did not become negative for a longer period of time (≥60 days, designated here as long-term nucleic acid test positive, LTNP), whereas other patients became negative for viral nucleic acid in a shorter period of time (≤45 days, designated as short-term nucleic acid test positive, STNP). We have found that TG (14:1/14:1/18:2) and FFA (4:0) were differentially expressed in LTNP and STNP. Conclusion: In summary, the integration of lipid information can help us discover novel biomarkers to identify asymptomatic individuals and further deepen our understanding of the molecular pathogenesis of COVID-19.

Thymosin α1 modulated the immune landscape of COVID-19 patients revealed by single-cell RNA and TCR sequencing.

BACKGROUND: The Coronavirus disease-19 (COVID-19) pandemic has posed a serious threat to global health. Thymosin α1 (Tα1) was considered to be applied in COVID-19 therapy. However, the data remains limited. METHODS: Participants with or without Tα1 treatment were recruited. Single cell RNA-sequencing (scRNA-seq) and T cell receptor-sequencing (TCR-seq) of the peripheral blood mononuclear cell (PBMC) samples were done to analyze immune features. The differential expression analysis and functional enrichment analysis were performed to explore the mechanism of Tα1 therapy. RESULTS: 33 symptomatic SARS-CoV-2-infected individuals (COV) and 11 healthy controls (HC) were enrolled in this study. The proportion of CD3+ KLRD1+ NKT, TBX21+ CD8+ NKT was observed to increase in COVID-19 patients with Tα1 treatment (COVT) than those without Tα1 (COV) (p = 0.024; p = 0.010). These two clusters were also significantly higher in Health controls with Tα1 treatment (HCT) than those without Tα1 (HC) (p = 0.016; p = 0.031). Besides, a series of genes and pathways related to immune responses were significantly higher enriched in Tα1 groups TBX21+ CD8+ NKT, such as KLRB1, PRF1, natural killer cell-mediated cytotoxicity pathway, chemokine signaling pathway, JAK-STAT signaling pathway. The increased TRBV9-TRBJ1-1 pair existed in both HCs and COVID-19 patients after Tα1 treatment. 1389 common complementarity determining region 3 nucleotides (CDR 3 nt) were found in COV and HC, while 0 CDR 3 nt was common in COVT and HCT. CONCLUSIONS: Tα1 increased CD3+ KLRD1+ NKT, TBX21+ CD8+ NKT cell proportion and stimulated the diversity of TCR clones in COVT and HCT. And Tα1 could regulate the expression of genes associated with NKT activation or cytotoxicity to promote NKT cells. These data support the use of Tα1 in COVID-19 patients.

Survival benefit of perioperative locoregional adjuvant treatment for hepatocellular carcinoma with portal vein tumor thrombosis: A systematic review and Bayesian network meta-analysis.

BACKGROUND: To identify the optimal strategy for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) by comparing the oncological prognosis of different perioperative locoregional adjuvant treatments. METHODS: Electronic database were searched for relevant studies. Overall survival (OS) and recurrence-free survival (RFS) were pooled by pairwise and network meta-analysis. RESULTS: Fourteen eligible trials with 1927 patients and covering four adjuvant treatments were included. All adjuvant therapies in combination with surgery were shown to be superior to surgery alone. Adjuvant therapy with radiotherapy had the lowest hazard ratio (HR) for both OS (HR: 0.38, 95% CrI: 0.25-0.57) and RFS (HR: 0.27, 95% CrI: 0.11-0.65) compared with other combination treatments, with estimated surface under the cumulative ranking of 93.2% and 82.7%, respectively. CONCLUSIONS: Perioperative locoregional adjuvant therapy provides OS benefits and reduces the risk of recurrence for patients suffering from HCC with PVTT. Radiotherapy is likely to be the most effective adjuvant regimen.

Transcriptome Analysis of Glycerin Regulating Reuterin Production of Lactobacillus reuteri.

Reuterin can be produced from glycerol dehydration catalyzed by glycerol dehydratase (GDHt) in Lactobacillus reuteri and has broad application prospects in industry, agriculture, food, and other fields as it is active against prokaryotic and eukaryotic organisms and is resistant to proteases and lipases. However, high concentrations of glycerin inhibit reuterin production, and the mechanism behind this phenomenon is not clear. To elucidate the inhibitory mechanism of glycerol on reuterin synthesis in L. reuteri and provide reference data for constructing an L. reuteri culture system for highly effective 3-hydroxypropionaldehyde synthesis, we used transcriptome-sequencing technology to compare the morphologies and transcriptomes of L. reuteri cultured in a medium with or without 600 mM of glycerol. Our results showed that after the addition of 600 mM of glycerol to the culture medium and incubation for 10 h at 37 °C, the culture medium of L. reuteri LR301 exhibited the best bacteriostatic effect, and the morphology of L. reuteri cells had significantly changed. The addition of 600 mM of glycerol to the culture medium significantly altered the transcriptome and significantly downregulated the transcription of genes involved in glycol metabolism, such as gldA, dhaT, glpK, plsX, and plsY, but significantly upregulated the transcription of genes related to D-glucose synthesis.

The role of electrostatic potential in the translocation of triangulene across membranes.

Triangulene and its derivatives show broad application prospects in the fields of biological imaging and biosensing. However, its interaction with cell membranes is still poorly studied. In this study, classical molecular dynamics simulations were used to adjust the electrostatic potential of triangulene to observe its interactions with cell membranes. We found that electrostatic potential not only affects the behavior as it enters the cell membrane, but also spatial distribution within the cell membrane. The angle distribution of inside-0 and all-0 triangulene when penetrating the membrane is more extensive than that of ESP triangulene. However, inside-0 triangulene could cross the midline of the cell membrane and prefers to stay in the upper leaflet, while all-0 triangulene and ESP triangulene can reach the lower leaflet. These findings can help us regulate the distribution of nanoparticles in cells, so as to design functional nanoparticles that conform to the requirements.

[Study on enhanced sensitivity to DNA damage in POLQ knocking-down salivary of adenoid cystic carcinoma-83 cells].

PURPOSE: To investigate the effects of POLQ inhibition on proliferation, colony formation, cell cycle, DNA damage and repair in salivary adenoid cystic carcinoma-83 (SACC-83) cell line. METHODS: POLQ knocking-down SACC-83 cells were constructed using short hairpin RNA (shRNA) transient transfection, and the inhibition efficiency was detected by qRT-PCR and Western blot. DNA damage in SACC-83 cells was induced by different concentration of DNA damage agent etoposide (VP-16-213), and the levels of γH2AX expression were detected by Western blot to evaluate DNA double-strain breaks. Under different concentration of etoposide-induced DNA damage condition, CCK-8 assay was used to evaluate the effect of POLQ inhibition on cell proliferation in SACC-83 cell line. Under etoposide-induced DNA damage condition, plate colony assay was performed to detect the effect of POLQ inhibition on cell clone formation ability in SACC-83 cell line, and flow cytometry was used to detect the effect of POLQ inhibition on cell cycle in SACC-83 cell line. Furthermore, under etoposide-induced DNA damage condition, Western blot was used to analyze POLQ, γH2AX, RAD51 and PARP1 protein expression. SPSS 20.0 software package was used for statistical analysis. RESULTS: The mRNA and protein expression of POLQ was inhibited by shRNA transient transfection. Increased γH2AX in SACC-83 was closely coupled with increased concentrations of etoposide. The results of CCK-8 assay showed that POLQ knocking-down suppressed cell proliferation ability in SACC-83 cell line, and the inhibitory effect was mitigated with increased concentration of etoposide(P＜0.001). The result of plate colony assay demonstrated that under etoposide-induced DNA damage condition, compared with the control group, POLQ knocking-down suppressed cell colony ability in SACC-83 cell line(P＜0.001). Moreover, the results of flow cytometry demonstrated that under etoposide-induced DNA damage conditions, compared with the control group, POLQ knocking-down induced S phase arrest(P＜0.01). Mechanistically, the results of Western blot showed that POLQ regulated DNA damage and repair by promoting expression of γH2AX(P＜0.05) and homologous recombination (HR) pathway-related protein RAD51 (P＜0.05), respectively, and down-regulating the alternative non-homologous end joining (alt-NHEJ) pathway-related protein PARP1(P＜0.01). CONCLUSIONS: POLQ knocking-down promotes the sensitivity of SACC-83 cell line to DNA damage.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

Computationally rational design of metal-involving halogen bonds with π-covalency: Structures and bonding analysis.

Traditional π-covalent interactions have been proved in the non-metal halogen bond adducts formed by chloride and halogenated triphenylamine-based radical cations. In this study, we have rationally designed two metal-involving halogen bond adducts with π-covalency property, such as [L1-Pd···I-PTZ]+ (i.e., 1) and [L2-Pd···I-PTZ]+ (i.e., 2), in which the square-planar palladium complexes serve as halogen bond acceptor and 3,7-diiodo-10H-phenothiazine radical cation (i.e., [I-PTZ]•+ ) acts as halogen bond donor. Noncovalent interaction analysis and quantum theory of atoms in molecules analysis revealed that there are notable halogen bond interactions along the Pd···I direction without genuine chemical bond formed in both designed adducts. Energy decomposition analysis together with natural orbital for chemical valence calculations were performed to gain insight into their bonding nature, which demonstrated the presence of remarkable π-covalent interactions and σ-covalent interactions in both 1 and 2. We therefore proposed a new strategy for building the metal-involving halogen bonds with π-covalency property, which will help the further development of new types of halogen bonds.

Fluorescent property of carbon dots extracted from cigarette smoke and the application in bio-imaging.

Cigarette smoke is one of the six major pollution sources in the room air. It contains large number of particles with size less than 10 nm. There exist carbon dots (CDs) in cigarette smoke which have strong fluorescence and with good bio-compatibility and low toxicity. CDs in cigarette smoke can be applied in bio-imaging which has great potential applications in the integration of cancer diagnosis and treatment. In this paper, CDs were extracted from cigarette smoke. Then, sodium borohydride was added to CDs aqueous solution for reduction and the reduced CDs (R-CDs) were used for biological cell imaging. The results indicate that the CDs with the particle size <10 nm in cigarette smoke are self-assembled by the polymerizated polycyclic aromatic hydrocarbons (PAHs) and ammonium nitrite which are disk nano-structure composed of sp2/sp3 carbon and oxygen/nitrogen groups or polymers. Sodium borohydride can reduce the carbonyl group on the surface of CDs to hydroxyl group and increase the ratio of the Na 1s ratio of the CDs from 1.86 to 7.42. The CDs can emit blue fluorescence under ultraviolet irradiation. After reduction, the R-CDS have the intensity of fluorescence 7.2 times than before and the fluorescence quantum yield increase from 6.13% to 8.86%. The photoluminescence (PL) wavelength of R-CDS have red-shift of 7 nm which was due to the increasing of Na element ratio. The onion epidermal cells labeled with R-CDs show that the CDs could pass through the cell wall into the cell and reach the nucleus. The cell wall and the nucleus could be clearly visualized. CDs also shows low toxicity to human bronchial epithelial cells (BEAS-2B) with good biological activity. The obtained results indicate that the CDs and R-CDs have good fluorescent property which could be used as bio-imaging agent.

Comparative analysis of dosimetry and predictive somatotype parameters of prone and supine whole-breast irradiation among Chinese women after breast-conserving surgery.

Purpose: Finding a better treatment position (prone or supine) for whole-breast irradiation for Chinese female patients diagnosed with breast cancer by identify the associations between predictive somatotype parameters and dosimetric gains. Materials and methods: Two volumetric-modulated arc therapy (VMAT) plans were deployed for whole-breast irradiation in supine and prone position with a total dose of 50 Gy in 25 fractions. Dose-volume parameters were compared and analysed both in the target volume and organs at risk, and equivalent uniform dose-based figure-of-merit (fEUD) models were further used to quantitatively evaluate the overall merits of the two plans. Body shape parameters, including body mass index (BMI), body surface area (BSA), breast shape, cup size, bust size and chest size, were collected. Anatomic features such as the central heart distance (CHD) were measured on supine CT. Spearman's correlation analysis, receiver operating characteristic (ROC) curve analysis, and the linear regression models were conducted. Results: Doses to the heart and left anterior descending coronary artery (LADCA) are greater in left-sided breast cancer (BC) patients in the prone position than in the supine position, and the opposite was true for right-sided BC patients (p<0.001). 19 of 63 patients (5 left-sided and 14 right-sided BC) achieved greater benefit from the prone position according to the fEUD score. Right-sided BC patients with a bust size ≥92.25 cm, drop-type breasts and cup size ≥B are very likely to benefit from prone-position radiotherapy. The CHD is significantly positively associated with △fEUD among right-sided BC patients (rho=0.506, p=0.004). Using a cut-off point of 2.215, the CHD had 71.4% sensitivity and 81.2% specificity in predicting a successful prone plan. Conclusions: Right-sided BC patients had better dosimetric gain in the prone position than left-sided BC patients. The CHD is an especially good and novel predictor that could help to select prone-benefitting right-sided BC patients.

A neutral vicinal silylene/phosphane supported six-membered C2PSiAu2 ring and a silver(I) complex.

This work presents the different coordination nature of the bidentate ligand towards gold and silver complexes. The reaction of 1 with AuClSMe2 in dichloromethane resulted in two gold atoms containing six-membered ring PhC(NtBu)2Si-Au⋯Au-PPh2C6H4 (2). Compound 2 exhibits intramolecular aurophilic interaction (2.9987(7) Å), which is further supported by quantum chemical calculations. Moreover, the reduction of aluminium adduct 3 with AgSbF6 affords insertion of silver cation [{PhC(NtBu)2SiF2}-C6H4(PPh2)-Ag-(PPh2)C6H4{PhC(NtBu)2SiF2}]AlCl4- (4) between two phosphane. In compound 4 only two P(III) of two molecules of 1 coordinates to Ag(I), while two Si(II) remains uncoordinated and gives oxidative addition of Fluorine.

Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations.

B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3-7 and IGKV2-24 enriched in the asymptomatic subjects, whereas IGHV3-13, IGHV3-23-IGHJ4, IGHV1-18-IGLV3-19, IGHV1-18-IGLV3-21, and IGHV1-18-IGLV3-25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3-23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3-13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections.

Identification of TCR repertoires in asymptomatic COVID-19 patients by single-cell T-cell receptor sequencing.

The T cell-mediated immune responses associated with asymptomatic infection (AS) of SARS-CoV-2 remain largely unknown. The diversity of T-cell receptor (TCR) repertoire is essential for generating effective immunity against viral infections in T cell response. Here, we performed the single-cell TCR sequencing of the PBMC samples from five AS subjects, 33 symptomatic COVID-19 patients and eleven healthy controls to investigate the size and the diversity of TCR repertoire. We subsequently analyzed the TCR repertoire diversity, the V and J gene segment deference, and the dominant combination of αß VJ gene pairing among these three study groups. Notably, we revealed significant TCR preference in the AS group, including the skewed usage of TRAV1-2-J33-TRBV6-4-J2-2 and TRAV1-2-J33-TRBV6-1-J2-3. Our findings may shed new light on understanding the immunopathogenesis of COVID-19 and help identify optimal TCRs for development of novel therapeutic strategies against SARS-CoV-2 infection.