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Purpose. To predict visual acuity (VA) 1 month after anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema (DME) by using machine learning. Methods. This retrospective study included 281 eyes with DME receiving intravitreal anti-VEGF treatment from January 1, 2019, to April 1, 2021. Eighteen features from electronic medical records and measurements data from OCT images were extracted. The data obtained from January 1, 2019, to November 1, 2020, were used as the training set; the data obtained from November 1, 2020, to April 1, 2021, were used as the validation set. Six different machine learning algorithms were used to predict VA in patients after anti-VEGF therapy. After the initial detailed investigation, we designed an optimization model for convenient application. The VA predicted by machine learning was compared with the ground truth. Results. The ensemble algorithm (linear regression + random forest regressor) performed best in VA and VA variance predictions. In the validation set, the mean absolute errors (MAEs) of VA predictions were 0.137-0.153 logMAR (within 7-8 letters), and the mean square errors (MSEs) were 0.033-0.045 logMAR (within 2-3 letters) for the 1-month VA predictions, respectively. For the prediction of VA variance at 1 month, the MAEs were 0.164-0.169 logMAR (within 9 letters), and the MSEs were 0.056-0.059 logMAR (within 3 letters), respectively. Conclusions. Our machine learning models could accurately predict VA and VA variance in DME patients receiving anti-VEGF therapy 1 month after, which would be much valuable to guide precise individualized interventions and manage expectations in clinical practice.

Piezoelectric aluminum nitride (AlN) thin film, as a commonly used material for high-frequency acoustic resonators, has been a research hotspot in the RF field. Doping Sc elements in AlN is one of most effective methods to improve the piezoelectricity of the material. In this work, the first principal calculation and Mori–Tanaka model are used to obtain the piezoelectric constants of AlN, ScAlN, and AlN/ScAlN composites. Then, five types of AlN/ScAlN thin films are prepared on 8 inch silicon substrates. The crystal quality, roughness, and stress distribution are measured to characterize the film quality. The results show that composite film can effectively solve the problem of abnormal grains and reduce the roughness. Finally, a lamb wave resonator with an AlN/Sc0.2Al0.8N composite working at 2.33 GHz is fabricated. The effective electromechanical coupling coefficient Keff2 is calculated to be 6.19%, which has the potential to design high-frequency broadband filters.

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, β-catenin, GSK3β, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/β-catenin and Hippo/YAP signaling pathways.

Redclaw crayfish (Cherax quadricarinatus) was introduced to China many years ago. In recent years, a breeding boom for C. quadricarinatus has been set off in China due to a breakthrough in key technology of seedling breeding. The size and growth rate of C. quadricarinatus vary greatly between female and male individuals, usually the size and growth rate of male individuals are bigger than that of female individuals. There is usually a certain linkage relationship between the sex traits of crustaceans and their own nutrition. In order to explore the linkage relationship between the sex traits of C. quadricarinatus and its nutritional components, this study measured and analyzed the muscle nutritional components of female and male individuals. The results showed that the meat yield rate of male individuals was significantly higher than that of females (p < 0.05), and the crude fat content was significantly lower than that for females (p < 0.05). The ratios of essential amino acids to total amino acids for females and males were 39.61% and 38.49%, respectively. The ratios of essential amino acids to non-essential amino acids were 79.69% and 75.66%, respectively, which far exceed FAO/WHO standards and both belong to high-quality protein. The total amount of flavor amino acids of male individuals was significantly higher than that of female individuals (p < 0.05). The total amount of polyunsaturated fatty acids and the polyunsaturated fatty acid eicosapentaenoic acid of males are both significantly higher than that of females (p < 0.05). Studies have shown that there are certain differences in nutrition between male and female individuals. Compared with female individuals, the meat yield rate, crude protein content, and edible value of the muscles of male individuals is higher.

Trehalose, as a non-reductive disaccharide, plays a vital role in plant growth and development and resistance to abiotic stress. Trehalose-6-phosphate synthase (TPS) is a key enzyme in the synthesis mechanism of trehalose and TPS1 genes play a crucial role in the response to abiotic stress in plants. However, it has rarely been reported that CaTPS1 responds to cold and salt stresses in pepper. To verify the function of CaTPS1 in response to cold and salt stresses, CaTPS1 was silenced by virus-induced gene silencing (VIGS). Subsequently, the expressions of CaTPS1, plant morphology and some physiological indexes were analyzed after cold and salt stresses in pepper. The results showed that the expression of CaTPS1 was significantly lower in CaTPS1-silenced (pTRV2-CaTPS1) plant than that in the non-VIGS (CK) and negative control (PTRV2-00) plants. The parameters of response to cold and salt stresses have changed accordingly. The chlorophyll content decreased, while the trehalose content, peroxidase (POD) activity, catalase (CAT) activity and ascorbate peroxidase (APX) activity increased in all treatments. However, these parameters of response to cold and salt stresses were significantly lower in pTRV2-CaTPS1 plant than in CK and PTRV2-00 plants. This study suggested that CaTPS1 was involved in the response to cold and salt stresses in pepper.

The arrival of the 5G era has promoted the need for filters of different bandwidths. Thin-film bulk acoustic resonators have become the mainstream product for applications due to their excellent performance. The Keff2 of the FBAR greatly influences the bandwidth of the filter. In this paper, we designed an AlN-based adjustable Keff2 FBAR by designing parallel capacitors around the active area of the resonator. The parallel capacitance is introduced through the support column structure, which is compatible with conventional FBAR processes. The effects of different support column widths on Keff2 were verified by finite element simulation and experimental fabrication. The measured results show that the designed FBAR with support columns can achieve a Keff2 value that is 25.9% adjustable.

The depletion of shallow groundwater has seriously affected the sustainable development of water resources in the North China Plain (NCP). Based on 556 well monitoring observations over a period of 13 years, we quantitatively evaluated the shallow groundwater sustainability in the NCP via various indices (e.g., the reliability, resilience, vulnerability, and sustainability indices), and further discussed the contribution of different drivers (including climatic and non-climatic factors). The main conclusions are summarized as follows: (1) the yearly trend of shallow groundwater shows a serious long-term deficit in the Piedmont Plain but is not significant in the East-Central Plain. (2) As for the sustainability of shallow groundwater in the NCP, the reliability is below the medium level (reliability < 0.5) in most areas and the ability of shallow aquifers to restore groundwater is very weak (resilience < 0.2), while the lack of groundwater storage in most shallow aquifers is not serious (vulnerability < 0.4). The final sustainability index (

Abstract Background To avoid destructive sampling for conservation and genetic assessment, we isolated the DNA of clam Cyclina sinensis from their feces. DNA electrophoresis and PCR amplification were used to determine the quality of fecal DNA. And we analyzed the effects of different conditions on the degradation of feces and fecal DNA. Results The clear fecal DNA bands were detected by electrophoresis, and PCR amplification using clam fecal DNA as template was effective and reliable, suggesting that clam feces can be used as an ideal material for noninvasive DNA isolation. In addition, by analyzing the effects of different environmental temperatures and soaking times on the degradation of feces and fecal DNA, we found that the optimum temperature was 4 °C. In 15 days, the feces maintained good texture, and the quality of fecal DNA was good. At 28 °C, the feces degraded in 5 days, and the quality of fecal DNA was poor. Conclusions The clam feces can be used as an ideal material for noninvasive DNA isolation. Moreover, the quality of fecal DNA is negatively correlated with environmental temperature and soaking time.

This pot experiment was to evaluate how salts (NaCl, Na2SO4) and alkali (Na2CO3+NaHCO3) affect the physiological and biochemical characteristics during the seedling stage of two cotton cultivars (salt-tolerant, L24; salt-sensitive, X45). Salt and alkali stress reduced seedling emergence rate, relative biomass, and chlorophyll content, however, the REC and MDA content increased. Salt and alkali stress increased markedly superoxide dismutase (SOD) activity. Peroxidase (POD) activity increased first and then decreased as the increase of salt and alkali stress. Catalase (CAT) activity initially increased and then decreased as NaCl stress increased. In addition, the SOD activity, REC, and MDA content was markedly higher in salt stress than that in alkali stress. The proline content of L24 was higher than that of X45 under salt and alkali stress. However, glycine betaine and soluble sugar content of L24 was lower than that of X45 under alkali stress. The REC and MDA content of L24 were lower than those of X45, however, the relative biomass, chlorophyll content, SOD, POD, CAT, and Pro were higher than those of X45. In conclusion, salt tolerant cotton cultivars may possess a superior protection effect by increasing antioxidant enzymes activity under salt and alkali stress.

Selective hydrogenolysis of biomass glycerol to propanediol is a promising route for the production of high-value chemicals but remains a challenge. Here, the authors find a PtCu single atom alloy catalyst exhibits remarkably boosted performance with a turnover frequency value of 2.6 × 103 molglycerol·molPtCu–SAA −1·h−1.

It is a promising treatment strategy to use an induction heating system for pipe lining, which can void the low efficiency and difficult temperature control of the traditional flame and hot air heating. In this study, a novel finite element model of pipe scanning induction heating was established, and the reliability of the model was verified through experiments. In addition, through the Plackett-Burman design, the main factors affecting the temperature fluctuation at 5 mm of the lining layer are analyzed. Finally, based on the analysis results, the system parameters were optimized by response surface method and the parameter configuration of the induction heating system with the minimum temperature fluctuation of 5 mm lining layer was obtained. The model established in this paper greatly reduces the calculation time of the electromagnetic induction heating finite element model of the moving magnetic field. It can be applied to the temperature information prediction of the lining induction heating where high-temperature accuracy is required and provides a reference for the characterization of the lining induction heating system and its application in low-temperature heat treatment, and the modeling strategy can be extended to the characterization of the temperature field evolution of any mobile heat source.

Alkali lignin-degrading Bacillus were isolated from forest soils in China and were identified as Bacillus subtilis TR-03 and Bacillus cereus TR-25 by 16S rDNA sequence analysis. Wherein TR-03 displayed optimal 26.72% alkali lignin (2 g/L) degradation at 7 days and 71.23% of Azure-B (0.01%) decolorization at 36 h of cultivation at 37°C. Ligninolytic enzyme analysis revealed that TR-03 was capable of depolymerizing alkali lignin effectively by the producing of lignin peroxidase and laccase, wherein higher laccase activity was cell-associated. At last, the physical and chemical changes of lignin via SEM and FTIR analysis was further observed to prove the lignin degradation by Bacillus subtilis TR-03.

This paper investigates the twisted wind effect on a typical super-tall building (500-m-tall square prism) by conducting pressure model wind tunnel tests. Two twisted wind fields (TWFs) with maximum yaw angles of approximately 30° and 20°, respectively, near the ground level were generated in the wind tunnel using a guide vane system, and the test results of wind pressure and wind load in TWFs were compared with those obtained in conventional wind fields (CWFs) with constant wind direction along the vertical axis. In particular, the distribution of extreme cladding pressure as well as the correlation and coherence of local wind loads are discussed in detail. It was observed that the mechanism of the structural dynamic responses, such as the vortex shedding, is greatly affected by TWFs. Both the distributions of mean and extreme cladding pressures in TWFs significantly differ from those in CWFs, especially on the windward and side facades. However, in terms of the amplitudes, the extreme wind pressure and the maximum wind load in TWFs do not noticeably exceed those in CWFs. This study aims to provide useful information for the wind-resistant design of future tall buildings.

Foxtail millet has attracted substantial attention in recent years because of its excellent properties as a cereal crop with high nutritional value. Although the cultivation area of foxtail millet keeps growing, the fundamental research into the nutritional and eating qualities of foxtail millet germplasm collections is limited. In this study, we performed a survey of protein content, amino acid composition and eating quality among a germplasm collection of foxtail millet accessions grown in different environments. Our results revealed 21 accessions with stable protein content under different environments. The correlation analysis further revealed that the protein content of the grains was affected by environmental and genotypic interactions. The further amino acid composition analyses suggested that higher protein content accessions have a better essential amino acid index, providing more nutritional value for human beings and animal feedstock. Moreover, the flavor-related amino acid content and other eating-quality trait analyses were also performed. The subordinative analysis suggested that B331 could be the best accession with high protein content and superior eating quality. Taken together, this study provides essential nutritional and eating-quality data on our germplasm collection of foxtail millets, and provides a core genetic resource from which to breed elite foxtail millet varieties in the future.

The atmospheric vapour pressure deficit (VPD) has been demonstrated to be a significant environmental factor inducing plant water stress and affecting plant photosynthetic productivity. Despite this, the rate-limiting step for photosynthesis under varying VPD is still unclear. In the present study, tomato plants were cultivated under two contrasting VPD levels: high VPD (3–5 kPa) and low VPD (0.5–1.5 kPa). The effect of long-term acclimation on the short-term rapid VPD response was examined across VPD ranging from 0.5 to 4.5 kPa. Quantitative photosynthetic limitation analysis across the VPD range was performed by combining gas exchange and chlorophyll fluorescence. The potential role of abscisic acid (ABA) in mediating photosynthetic carbon dioxide (CO2) uptake across a series of VPD was evaluated by physiological and transcriptomic analyses. The rate-limiting step for photosynthetic CO2 utilisation varied with VPD elevation in tomato plants. Under low VPD conditions, stomatal and mesophyll conductance was sufficiently high for CO2 transport. With VPD elevation, plant water stress was gradually pronounced and triggered rapid ABA biosynthesis. The contribution of stomatal and mesophyll limitation to photosynthesis gradually increased with an increase in the VPD. Consequently, the low CO2 availability inside chloroplasts substantially constrained photosynthesis under high VPD conditions. The foliar ABA content was negatively correlated with stomatal and mesophyll conductance for CO2 diffusion. Transcriptomic and physiological analyses revealed that ABA was potentially involved in mediating water transport and photosynthetic CO2 uptake in response to VPD variation. The present study provided new insights into the underlying mechanism of photosynthetic depression under high VPD stress.

Many basic helix-loop-helix transcription factors (TFs) have been reported to promote anthocyanin biosynthesis in numerous plant species, but little is known about bHLH TFs that inhibit anthocyanin accumulation. In this study, SmbHLH1 from Solanum melongena was identified as a negative regulator of anthocyanin biosynthesis. However, SmbHLH1 showed high identity with SmTT8, which acts as a SmMYB113-dependent positive regulator of anthocyanin-biosynthesis in plants. Overexpression of SmbHLH1 in eggplant caused a dramatic decrease in anthocyanin accumulation. Only the amino acid sequences at the N and C termini of SmbHLH1 differed from the SmTT8 sequence. Expression analysis revealed that the expression pattern of SmbHLH1 was opposite to that of anthocyanin accumulation. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that SmbHLH1 could not interact with SmMYB113. Dual-luciferase assay demonstrated that SmbHLH1 directly repressed the expression of SmDFR and SmANS. Our results demonstrate that the biological function of bHLHs in anthocyanin biosynthesis may have evolved and provide new insight into the molecular functions of orthologous genes from different plant species.

The human HSP70 family is a type of heat shock protein (HSP), consisting of 13 members encoded by the HSPA genes. HSPs play important roles in regulating cellular responses and functions during carcinogenesis, but their relationship with colon cancer is unclear. In our study, we found that the expressions of HSPA1B, HSPA4, HSPA5, HSPA6, HSPA8, HSPA9, HSPA13, and HSPA14 were significantly increased, while those of HSPA1A, HSPA2, HSPA7, and HSPA12B were significantly decreased in colon cancer tissues. The expression of HSPA gene family members was associated with some clinicopathological characteristics, including age, gender, TNM stage, pathological stage, and CEA level. Furthermore, the Kaplan–Meier method and Cox regression analysis showed that high HSPA1A, HSPA1B, and HSPA7 expressions were related to unfavorable survival, and high HSPA9 was associated with favorable survival. The relationships between HSPA1A and HSPA9 expression and survival were validated in the GEO dataset, and the HSPA1A and HSPA9 protein expression differences between colon cancer tissues and normal tissues were validated in the UALCAN database. Methylation of HSPA1A and HSPA9 was also analyzed, and it was found that the methylation of the HSPA1A promoter was significantly increased, and the methylation of the HSPA9 promoter was significantly decreased in colon cancer tissues. Increasing the methylation level of the HSPA1A gene and decreasing the methylation level of HSPA9 were related to favorable prognosis. The expression difference of HSPA1A/HSPA1B/HSPA7/HSPA9 was verified in colon cancer cell lines and colonic epithelial cells. Gene ontology analysis was used to screen signal pathways related to HSPA1A-, HSPA1B-, HSPA7-, and HSPA9- high phenotype. In summary, the increased expressions of HSPA1A1, HSPA1B, and HSPA7 were associated with poor prognosis, while that of HSPA9 was related to favorable prognosis for colon cancer patients.

Inducible regulatory T (iTreg) cells play a central role in immune suppression. As iTreg cells are differentiated from activated T (Th0) cells, cell metabolism undergoes dramatic changes, including a shift from fatty acid synthesis (FAS) to fatty acid oxidation (FAO). Although the reprogramming in fatty acid metabolism is critical, the mechanism regulating this process during iTreg differentiation is still unclear. Here we have revealed that the enzymatic activity of ATP-citrate lyase (ACLY) declined significantly during iTreg differentiation upon transforming growth factor β1 (TGFβ1) stimulation. This reduction was due to CUL3-KLHL25-mediated ACLY ubiquitination and degradation. As a consequence, malonyl-CoA, a metabolic intermediate in FAS that is capable of inhibiting the rate-limiting enzyme in FAO, carnitine palmitoyltransferase 1 (CPT1), was decreased. Therefore, ACLY ubiquitination and degradation facilitate FAO and thereby iTreg differentiation. Together, we suggest TGFβ1-CUL3-KLHL25-ACLY axis as an important means regulating iTreg differentiation and bring insights into the maintenance of immune homeostasis for the prevention of immune diseases.

Chinese tongue sole (Cynoglossus semilaevis) has a ZZ/ZW sex determination system, but the genotypic female (ZW) can be sex-reversed into phenotypic males, namely, pseudomales. Pseudomale fish can produce only Z-type sperm but not W sperm. However, the molecular mechanism is unclear. To screen the key genes involved in pseudomale sperm abnormalities, we analysed the transcriptomic profiles of pseudomale and male sperm. In comparison to male sperm, 592 differentially expressed genes (DEGs) were identified in pseudomale sperm, including 499 upregulated and 93 downregulated genes. KEGG analysis indicated that the FoxO signalling pathway, especially the foxo3a and foxo6-like genes, may play an important role in spermatogenesis. The DEGs were mainly distributed on sex chromosomes, with 158 downregulated genes on the Z chromosome and 41 upregulated genes on the W chromosome. A specific area (14–15 M) on the Z chromosome was identified, which enriched eight DEGs inside the ~1 M region. In addition, there were five gene alleles on the sex chromosomes, which showed the opposite transcription pattern (upregulated for the W allele, downregulated for the Z allele). This study has provided valuable data for screening candidate genes involved in the pseudomale sperm abnormality.

Flow boiling in microchannels is one of the promising techniques for heat dissipation occurred in micro devices. However, the rapid bubble growth must be suppressed, which leads to serious boiling instabilities, high pressure drop, and low heat transfer coefficient. The addition of porous hydrophobic membrane has proven an effective method to remove the vapor in-site in the literature. However, the effects of heat sink’s topological structures on the vapor venting are still a research gap. The present study experimentally investigates the influence of Polytetrafluoroethylene (PTFE) membrane on fluid flow pattern, pressure drop, vapor venting performance, and heat transfer characteristics of flow boiling in the continuous and segmented heat sinks. Results show that the vapor venting membrane can reduce the pressure drop and increase the heat transfer coefficient effectively by decreasing the exit vapor quality, especially in combination with the segmented structures. The interconnection area as a space for bubble growth and coalescence is beneficial for vapor venting due to increased vapor pressure and quantity. Following the enhanced vapor discharge, the fluctuation of pressure drop is further weakened, which is conducive for the safe operation of heat sink.

Exopolysaccharide (EPS) from probiotic Enterococcus hirae WEHI01 was isolated and purified by anion exchange chromatography and gel chromatography, the results of which show that the EPS consists of four fractions, namely I01-1, I01-2, I01-3, and I01-4. As the main purification components, I01-2 and I01-4 were preliminarily characterized for their structure and their immunomodulatory activity was explored. The molecular weight of I01-2 was 2.28 × 104 Da, which consists mainly of galactose, and a few other sugars including glucose, arabinose, mannose, xylose, fucose, and rhamnose, while the I01-4 was composed of galactose only and has a molecular weight of 2.59 × 104 Da. Furthermore, the results of an evaluation of immunomodulatory activity revealed that I01-2 and I01-4 could improve the viability of macrophage cells, improve phagocytosis, boost NO generation, and encourage the release of cytokines including TNF-α and IL-6 in RAW 264.7 macrophages. These results imply that I01-2 and I01-4 could improve macrophage-mediated immune responses and might be useful in the production of functional food and medications.

Tumor progression includes the obtainment of progenitor and stem cell-like features and the gradual loss of a differentiated phenotype. Stemness was defined as the potential for differentiation and self-renewal from the cell of origin. Previous studies have confirmed the effective application of stemness in a number of malignancies. However, the mechanisms underlying the growth and maintenance of multiple myeloma (MM) stem cells remain unclear. We calculated the stemness index for samples of MM by utilizing a novel one-class logistic regression (OCLR) machine learning algorithm and found that mRNA expression-based stemness index (mRNAsi) was an independent prognostic factor of MM. Based on the same cutoff value, mRNAsi could stratify MM patients into low and high groups with different outcomes. We identified 127 stemness-related signatures using weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional annotation and pathway enrichment analysis indicated that these genes were mainly involved in the cell cycle, cell differentiation, and DNA replication and repair. Using the molecular complex detection (MCODE) algorithm, we identified 34 pivotal signatures. Meanwhile, we conducted unsupervised clustering and classified the MM cohorts into three MM stemness (MMS) clusters with distinct prognoses. Samples in MMS-cluster3 possessed the highest stemness fractions and the worst prognosis. Additionally, we applied the ESTIMATE algorithm to infer differential immune infiltration among the three MMS clusters. The immune core and stromal score were significantly lower in MMS-cluster3 than in the other clusters, supporting the negative relation between stemness and anticancer immunity. Finally, we proposed a prognostic nomogram that allows for individualized assessment of the 3- and 5-year overall survival (OS) probabilities among patients with MM. Our study comprehensively assessed the MM stemness index based on large cohorts and built a 34-gene based classifier for predicting prognosis and potential strategies for stemness treatment.

Background: SARS-CoV-2 infection was referred to sympathetic hyperactivity, which might increase the susceptibility of neuraxial anesthesia-related hypotension resulted from sympathetic inhibition. We conducted a multicenter, retrospective, propensity score matched (PSM) cohort study to determine whether COVID-19 parturients have an increased risk of hypotension after neuraxial anesthesia for cesarean delivery.Methods: Clinical data of COVID-19 parturients were collected from the electronic medical records from 1th January to 31th May, 2020 in three hospitals of Hubei Province, China. Information of Control parturients (without COVID-19) were obtained at the same institutions over a similar period in 2019. All American Society of Anaesthesiologists (ASA) Physical Status II full termed pregnant women who received cesarean delivery under neuraxial anesthesia were included. The primary objective was to obtain and compare the incidence of neuraxial anesthesia-related hypotension. Secondary objectives were the analysis of anesthetic implementation and administration, intraoperative maternal vital signs and adverse reactions, and neonatal Apgar scores at 1 and 5 min after delivery. The clinical characteristics of COVID-19 parturients were also analyzed. PSM was derived to balance the predictors for neuraxial anesthesia-related hypotension based on previous studies.Results: In present study, 101 COVID-19 parturients and 186 Control parturients were derived from 1,403 cases referenced to propensity score matching. The incidence of neuraxial anesthesia-related hypotension was 57.4% in COVID-19 parturients and 41.9% in Control parturients with an incidence risk ratio (IRR) of 1.37 (95% CI 1.08–1.74; P = 0.012; post-hoc Cramér's V = 0.15) in the PSM cohort. The incidences of nausea, vomiting, dizziness, and shaking were significantly higher in the COVID-19 group than Control group (48.5 vs. 17.2%, P < 0.001; 10.9 vs. 4.3%, P = 0.03; 18.8 vs. 3.2%, P < 0.001; 51.5 vs. 18.3%, P < 0.001; respectively). The Apgar scores at 1 min was significantly lower in newborns from COVID-19 parturients than that in Control babies (P = 0.04).Conclusions: An increased risk of neuraxial anesthesia-related hypotension in COVID-19 parturients undergoing cesarean delivery should be stressed.

Metal ions are heavily involved in the membrane potential and intracellular activities of cells. Increasing evidences have shown that it is critical to evaluate the ion levels and monitor their dynamic changes in the brain for the diagnosis of neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington disease, amyotrophic lateral sclerosis, and so on. Herein, the roles of metal ions in the occurrence and development of NDDs are intensively discussed, and the recent advances in probes and sensors for ion‐level detection are summarized. Finally, the further applications of ingenious ion‐selective probes and sensors are outlined, highlighting the future opportunities for the metal ion‐based diagnosis of NDDs.

Abstract In this work, using DNA and exonuclease-I (Exo-I) as signal amplification strategy, a novel and facile electrochemical aptasensor was constructed for fumonisin B1 (FB1) detection. The G-rich complementary DNA (cDNA) was immobilized onto the electrode surface. Then, aptamer of FB1 was hybridized with cDNA to form double-stranded DNA. In the absence of FB1, double-stranded DNA and G-rich cDNA on the electrode surface promoted effectively methylene blue (MB) enrichment and amplified the initial electrochemical response. In the presence of FB1, the combination of aptamer and FB1 led to the release of aptamer from the electrode surface and the expose of 3′ end of single-stranded cDNA. When Exo-I was added onto the electrode surface, the single-stranded cDNA was degraded in the 3′–5′ direction. The decrease of double-stranded DNA and G-rich cDNA resulted in the less access of MB to the electrode surface, which decreased the electrochemical signal. The experimental conditions including incubation time of FB1, the amount of Exo-I and incubation time of Exo-I were optimized. Under the optimal conditions, the linear relationship between the change of peak current and the logarithmic concentration of FB1 was observed in the range of 1.0 × 10−3–1000 ng mL−1 with a low limit of detection of 0.15 pg mL−1. The experimental results showed that the prepared aptasensor had acceptable specificity, reproducibility, repeatability and stability. Therefore, this proposed aptasensor has a potential application in the food safety detection.

Itaconic acid (IA) is a precursor of various chemicals, which has been on the US Department of Energy’s list of the top 12 platform chemicals that can potentially be produced from biomass. The IA is mainly produced through a bio-fermentation method with sugar as raw material. However, the high cost and low yield restrict the industrial application of the IA. This review summarized research advances in the IA production from alternative substrates. In particular, the types of substrates as well as existing problems in the IA fermentation, strain breeding, and process regulation were discussed. And it is pointed that decreasing the price of the IA with alternative substrates and increasing the titer through genetic engineering should be further focused on to support the industrialization of the IA.

Abstract GDP-l-fucose, the key substrate for fucosyloligosaccharide biosynthesis, has been synthesized via a de novo pathway in bacteria. In the present study, genes for GDP-l-fucose biosynthesis were cloned into the expression vector pET-28a (+) to construct five E. coli strains, with recombinant enzymes being purified by using Ni–NTA chromatography. Following optimization of the 3-step reaction, Glk, ManB and ManC were added to the reaction mixture, after which Gmd and WcaG were added to overcome feedback inhibition from the end-product to produce GDP-l-fucose at 178.6 mg/l, with a yield of 14.1%. Our studies provide the basis for using cell-free enzyme production of GDP-l-fucose.

Abstract Background The high mortality of patients with non-small cell lung cancer (NSCLC) emphasizes the necessity of identifying a robust and reliable prognostic signature for NSCLC patients. This study aimed to identify and validate a prognostic signature for the prediction of both disease-free survival (DFS) and overall survival (OS) of NSCLC patients by integrating multiple datasets. Methods We firstly downloaded three independent datasets under the accessing number of GSE31210, GSE37745 and GSE50081, and then performed an univariate regression analysis to identify the candidate prognostic genes from each dataset, and identified the gene signature by overlapping the candidates. Then, we built a prognostic model to predict DFS and OS using a risk score method. Kaplan–Meier curve with log-rank test was used to determine the prognostic significance. Univariate and multivariate Cox proportional hazard regression models were implemented to evaluate the influences of various variables on DFS and OS. The robustness of the prognostic gene signature was evaluated by re-sampling tests based on the combined GEO dataset (GSE31210, GSE37745 and GSE50081). Furthermore, a The Cancer Genome Atlas (TCGA)-NSCLC cohort was utilized to validate the prediction power of the gene signature. Finally, the correlation of the risk score of the gene signature and the Gene set variation analysis (GSVA) score of cancer hallmark gene sets was investigated. Results We identified and validated a six-gene prognostic signature in this study. This prognostic signature stratified NSCLC patients into the low-risk and high-risk groups. Multivariate regression and stratification analyses demonstrated that the six-gene signature was an independent predictive factor for both DFS and OS when adjusting for other clinical factors. Re-sampling analysis implicated that this six-gene signature for predicting prognosis of NSCLC patients is robust. Moreover, the risk score of the gene signature is correlated with the GSVA score of 7 cancer hallmark gene sets. Conclusion This study provided a robust and reliable gene signature that had significant implications in the prediction of both DFS and OS of NSCLC patients, and may provide more effective treatment strategies and personalized therapies.

Aim: Natural killer (NK) cells, as key regulatory cells, accumulate at the maternal-fetal interface in large numbers. This study explored the effect of miR-30e on regulating the activity and function of peripheral blood NK cells (PB-NK cells) and decidua NK cells (D-NK cells) by targeting PRF1 in immune tolerance of maternal-fetal interface.Methods: Expressions of miR-30e in PB and decidua tissues from 49 patients with recurrent spontaneous abortion and 52 normal pregnant women were measured using PCR. NK cells were isolated from PB and decidua tissues and identified by flow cytometry (FCM). In PB-NK cells and D-NK cells activated by IFN-α, expressions of miR-30e and PRF1 were determined by PCR and Western blot. Negative controls of miR-30e mimics/inhibitors and siRNA against PRF1 were transfected in PB-NK cells and D-NK cells. Expressions of miR-30e and PRF1 were determined and their relationship was verified. Expressions of KIR2DL1, NKp44, IFN-γ, TNF-α, IL-4 and IL-10 were determined by FCM. Cytotoxicity kit was used to identify the cytotoxicity of NK cells. PCR and ELISA were employed to measure expression of VEGF, Ang-2 and PGF in D-NK cells.Results: After activation by IFN-α, D-NK cells and PB-NK cells showed decreased miR-30e expression and increased PRF1 expression in normal non-pregnant women. PRF1 is a target gene of miR-30e and miR-30e negatively regulated PRF1 expression. The treatment of miR-30e mimics elevated KIR2DL1 expression and decreased NKp44 expression in PB-NK or D-NK cells. Moreover, up-regulation of miR-30e expression suppressed cytotoxicity, corresponding to increased expression of IL-4and IL-10 and reduced expression of IFN-γ and TNF-α in PB-NK and D-NK cells, as well as enhanced expression of VEGF, Ang-2 and PGF in D-NK cells. Transfection of miR-30e inhibitors could reverse the tendencies.Conclusion: Up-regulated miR-30e can reduce the cytotoxicity of PB-NK cells and D-NK cells by targeting PRF1, whereby inhibiting Th1 tolerance phenotype and inducing Th2 immunodominance. miR-30e may be contributive to creating a micro-immune tolerance environment of maternal-fetal interface.

The hydroturbine runner is the core of the whole hydroelectric generating unit, which is employed to transform water energy into mechanical energy. In the process of service, the runner frequently suffers from abrasion due to erosion and cavitation. Defects are usually repaired by welding. To acquire suitable weld cladding repair process parameters, a combination of experimental and numerical simulation was applied to investigate the temperature and weld residual stress distribution in the repair zone under the different welding repair approaches. The results illustrate that the temperature and welding residual stress distribution of the blade and the shroud are out of symmetry, the temperature conduction rate is faster on the blade side, and the high-stress zone is predominantly concentrated in the weld and its adjacent area. When the preheating temperature is up to 150 °C, the peak value of welding residual stress reaches a minimum of 796.29 MPa. The welding sequence can adjust the distribution trend of welding residual stresses. The welding sequence of three-stage welding can effectively reduce the welding residual stresses near the shroud at the water outlet side of the blade. The results of the study will provide theoretical guidance for the welding repair of hydraulic turbine runners.

Auxin response factors (ARFs) are important plant transcription factors that are differentially expressed in response to auxin and various abiotic stresses. ARFs play important roles in mediating plant growth and stress responses; however, these factors have not been studied in eggplants. In this study, genome–wide identification and the functional analysis of the ARF gene family in eggplants (Solanum melongena L.) were performed. A total of 20 ARF (SmARF) genes were identified and phylogenetically classified into three groups. Our analysis revealed four functional domains and 10 motifs in these proteins. Subcellular localization showed that the SmARFs localized in the nucleus. To investigate the biological functions of the SmARFs under 2,4–D and salt stress treatments, quantitative real–time RT–PCR (qRT–PCR) was conducted. Most SmARF genes exhibited changes in expression in response to 2,4–D treatments in the flowers, especially SmARF4 and 7B. All SmARF genes quickly responded to salt stress, except SmARF17 and 19 in leaves, SmARF1A and 7B in roots, and SmARF2A, SmARF7B, and SmARF16B in stems. These results helped to elucidate the role of ARFs in auxin signaling under 2,4–D and salt stress in eggplants.

The prediction skill of Arctic Oscillation (AO) in the decadal experiments with the Beijing Climate Center Climate System Model version 1.1 (BCC_CSM1.1) is assessed. As compared with the observations and historical experiments, the contribution of initialization for climate model to predict the seasonal scale AO and its interannual variations is estimated. Results show that the spatial correlation coefficient of AO mode simulated by the decadal experiment is higher than that in the historical experiment. The two groups of experiments reasonably reproduce the characteristics that AO indices are the strongest in winter and the weakest in summer. Compared with historical experiments, the correlation coefficient of the monthly and winter AO indices are higher in the decadal experiments. In particular, the correlation coefficient of monthly AO index between decadal hindcast and observation reached 0.1 significant level. Furthermore, the periodicity of the monthly and spring AO indices are achieved only in the decadal experiments. Therefore, the initial state of model is initialized by using sea temperature data may help to improve the prediction skill of AO in the decadal prediction experiments to some extent. Keywords: BCC_CSM1.1, Climate model, Decadal, Arctic oscillation, Hindcast

Abstract Background Plant phospholipase D (PLD), which can hydrolyze membrane phospholipids to produce phosphatidic acid (PA), a secondary signaling molecule, has been proposed to function in diverse plant stress responses. Both PLD and PA play key roles in plant growth, development, and cellular processes. PLD was suggested to mediate the regulation of stomatal movements by abscisic acid (ABA) as a response to water deficit. In this research, we characterized the roles of the cucumber phospholipase D alpha gene (CsPLDα, GenBank accession number EF363796) in the growth and tolerance of transgenic tobacco (Nicotiana tabacum) to drought stress. Results The CsPLDα overexpression in tobacco lines correlated with the ABA synthesis and metabolism, regulated the rapid stomatal closure in drought stress, and reduced the water loss. The NtNCED1 expression levels in the transgenic lines and wild type (WT) were sharply up-regulated after 16 days of drought stress compared with those before treatment, and the expression level in the transgenic lines was significantly higher than that in the WT. The NtAOG expression level evidently improved after 8 and 16 days compared with that at 0 day of treatment and was significantly lower in the transgenic lines than in the WT. The ABA content in the transgenic lines was significantly higher than that in the WT. The CsPLDα overexpression could increase the osmolyte content and reduce the ion leakage. The proline, soluble sugar, and soluble protein contents significantly increased. By contrast, the electrolytic leakage and malondialdehyde accumulation in leaves significantly decreased. The shoot and root fresh and dry weights of the overexpression lines significantly increased. These results indicated that a significant correlation between CsPLDα overexpression and improved resistance to water deficit. Conclusions The plants with overexpressed CsPLDα exhibited lower water loss, higher leaf relative water content, and heavier fresh and dry matter accumulation than the WT. We proposed that CsPLDα was involved in the ABA-dependent pathway in mediating the stomatal closure and preventing the elevation of intracellular solute potential.

Background: Oncolytic virotherapy with vaccinia virus (VV) can lead to effective anti-tumor immunity by turning “cold” tumors into “hot” tumors. However, its therapeutic potential is affected by the tumor's local immunosuppressive tumor microenvironment (TME). Therefore, it is necessary to explore the use of immune checkpoint inhibitors to arm oncolytic VVs to enhance their anti-tumor efficacy. Methods: A novel recombinant oncolytic VV, VV-α-TIGIT, which encoded a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT) was generated by homologous recombination with a shuttle plasmid. The anti-tumor efficacy of the VV-α-TIGIT was investigated in several subcutaneous and ascites tumor models. Findings: The functional α-TIGIT was sufficiently produced and secreted by tumor cells infected with VV-α-TIGIT, which effectively replicated in tumor cells leading to significant oncolysis. Intratumoral injection of VV-α-TIGIT improved anti-tumor efficacy in several murine subcutaneous tumor models compared to VV-Control (without α-TIGIT insertion). Intraperitoneal injection of VV-α-TIGIT achieved approximately 70% of complete tumor regression in an ascites tumor model. At the same time, treatment with VV-α-TIGIT significantly increased the recruitment and activation of T cells in TME. Moreover, the in vivo anti-tumor activity of VV-α-TIGIT was largely dependent on CD8+ T cell-mediated immunity. Finally, the tumor-bearing mice cured of VV-α-TIGIT treatment resisted rechallenge with the same tumor cells, suggesting a long-term persistence of tumor-specific immunological memory. Interpretation: The recombinant oncolytic virus VV-α-TIGIT successfully combines the advantages of oncolytic virotherapy and intratumorally expression of immune checkpoint inhibitor against TIGIT. This novel strategy can provide information on the optimal design of novel antibody-armed oncolytic viruses for cancer immunotherapy. Funding: This work was supported by the National Natural Science Foundation of China (81773255, 81472820, and 81700037), the Science and Technology Innovation Foundation of Nanjing University (14913414), and the Natural Science Foundation of Jiangsu Province of China (BK20171098).

Accumulating evidence indicates that N6-methyladenosine (m6A), which directly regulates mRNA, is closely related to multiple biological processes and the progression of different malignancies, including breast cancer (BC). Studies of the aberrant expression of m6A mediators in BC revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Bcl-2 and the PI3K/Akt pathway, among others. Several regulators that target m6A have been shown to have anticancer effects. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis. However, the exact mechanism by which m6A modifications are regulated by FTO inhibitors remains unknown. m6A modifications in BC have only been preliminarily studied, and their mechanisms require further investigation.

In order to rationally develop and utilize a Ta–Nb–Li–Rb rare metal deposit in Jiangxi Province, the mineralogical characteristics of the ore, such as chemical composition, mineral composition, modes of occurrence of major elements, and dissemination characteristics of major minerals, were investigated in detail based on optical microscopy analysis, chemical analysis, X-ray diffraction analysis, artificial panning, mineral liberation analysis, and electron probe microanalysis. The results reveal that the main useful elements in the ore are tantalum, niobium, lithium, and rubidium. Niobium and tantalum are mainly found in the mineral form of columbite. Columbite has particle sizes ranging from 0.5 mm to 0.012 mm, with the most common sizes being 0.3 to 0.044 mm. Intergranular dispersion accounts for 73.92% of the embedding in columbite, whereas inclusions account for 26.08%. Lithium is found mostly in zinnwaldite, while rubidium is found primarily in feldspar and zinnwaldite, both in a homogenous distribution. The beneficiation evaluation of this ore was conducted based on the mineralogical characteristic, and it indicates that the tantalum-niobium–lithium–rubidium rare metal resources, as well as the feldspar and quartz non-metallic resources in the ore, can be effectively and comprehensively recovered using gravity, magnetic, and flotation separation methods. A staged grinding and separating process was adopted which could produce tantalum–niobium mineral concentrates (18.34% Ta2O5 at a recovery of 47.65% and 41.33% Nb2O5 at a recovery of 69.96%), zinnwaldite concentrate (2.41% Li2O and 0.80% Rb2O at a recovery of 81.82%) and other concentrates such as cassiterite, topaz, galena, sphalerite, and feldspar. This study provides suggestions for the rational development and utilization of the deposit and provides a reasonable level of recovery prediction.

Efficient capture of particulate matter in the smoke mainstream using low-cost filter pads is important for cost-effective analysis of mainstream smoke. The Cambridge filter pad (CFP) is the standard material for the collection of particulate matter in the mainstream. In this work, we report a low-cost alternative to CFP, which is composed of a cellulose acetate fiber (CAF) interlayer and two cotton fiber (CF) layers on both sides. The CF/CAF/CF filter exhibited high affinity toward typical tobacco additives such as glycerol and glycerol triacetate. In addition, the CF/CAF/CF filter had a favorable porous structure for the trapping of particulate matter. Due to these beneficial features, the CF/CAF/CF filter exhibited improved particulate matter trapping performance. These results suggest that the as-developed CF/CAF/CF filter could be a low-cost alternative to CFP.

Purpose: To assess the survival outcomes of patients with metastatic prostate cancer (mPCa) who undergo greater cytoreductive radiotherapy in a real-world clinical practice and determine their prognostic factors.Methods: We performed a retrospective study of 160 patients with mPCa who underwent cytoreductive radiotherapy between 2009 and 2018 at a single institution. The degree of the cytoreductive burden was calculated for each patient. Overall survival (OS) was calculated from the date of detection of metastases. Variables associated with prostate-specific antigen (PSA) response and OS were evaluated via univariate and multivariate analyses.Results: The median follow-up period was 47.2 months. The median OS was 42.3 months with a 5-year OS rate of 37.9%. The PSA levels of 90 patients (56.7%) decline by > 50% after radiotherapy. The 5-year OS rates of patients who underwent total, major, and minor cytoreductive radiotherapy were 53.4, 38.2, 17.6%, respectively; the corresponding median OS intervals were 62.5, 41.0, and 24.4 months, respectively (P < 0.001). A greater extent of cytoreduction (P < 0.05), lower PSA at radiotherapy initiation [hazard ratio 0.51, 95% confidence interval [CI] 0.33–0.78; P = 0.002] and better PSA response [hazard ratio 0.47, 95% CI 0.30–0.72; P < 0.001] were independent factors associated with superior OS. A high metastatic burden (as defined in the CHAARTED trial) was the only independent predictor of a poorer PSA response (odds ratio 0.36, 95% CI 0.19–0.69; P = 0.002). Grade 2 late gastrointestinal and genitourinary toxicities were observed in 3 and 2 patients, respectively, and only 1 patient had grade 3 late gastrointestinal toxicity.Conclusion: Cytoreductive radiotherapy is effective and safe in select patients with mPCa. Greater cytoreduction, together with lower PSA at radiotherapy initiation and improved PSA response are favorable prognostic factors. Further studies are needed to confirm our findings.

Increasing evidence indicates that the Aquaporin1 (AQP1) aberrant expression may be related to a wide variety of human cancers, including breast cancer (BC). In the present study, we explore the effects and possible mechanism of miR-3194-3p on the biological behaviors of BC. At first, miR-3194-3p is found to modulate AQP1 expression targeting the 3′-UTR using miRNA target prediction algorithms. MiR-3194-3p expression is markedly downregulated, and AQP1 expression is upregulated in BC tissues compared with adjacent normal breast tissues. Moreover, the differential expression of miR-3194-3p and AQP1 are observed in four BC cells with different malignancy degree. Meanwhile, a significant negative correlation between AQP1 and miR-3194-3p expressions in tumor tissues from 30 BC patients is revealed. miR-3194-3p mimic remarkably inhibits cell proliferation, migration, and invasion as well as promotes apoptosis in MDA-MB-231 cells while miR-3194-3p inhibitors exert an opposite role in MCF-7 cells. Dual-luciferase reporter system demonstrates that AQP1 is a direct target gene of miR-3194-3p. Overexpression of AQP1 by pBABE-puro-AQP1 vector partially abrogates the effect of miR-3194-3p mimic in MDA-MB-231 cells. In short, our results suggest that miR-3194-3p suppresses BC cell proliferation, migration, and invasion by targeting AQP1, providing a novel insight into BC tumorigenesis and treatment.

Background: Local anesthesia (LA) is widely used in knee arthroscopic surgery but not in ankle arthroscopy. Objective: To understand the effectiveness and safety of LA combined with ropivacaine in pain control for ankle arthroscopy. Study Design: Retrospective cohort. Methods: We retrospectively collected data for patients who underwent ankle arthroscopy from April 2012 to April 2017. Patients were grouped by anesthesia method: LA, LA with ropivacaine (LA+R), spinal anesthesia (SA), and SA with ropivacaine (SA+R). Intra- and postoperative visual analog scale (VAS) scores, complications, doses of supplemental pain medication, hospitalization cost and duration, and satisfaction with pain control during hospitalization were analyzed. Results: The study included 276 patients (LA: 93; LA+R: 124; SA: 31; SA+R: 28). The LA and LA+R groups had significantly higher intraoperative VAS scores (LA vs. SA, p = 0.001; LA vs. SA+R, p = 0.002; LA+R vs. SA, p = 0.00; LA+R vs. SA+R, p = 0.00), but fewer complications, than the SA and SA+R groups. The LA+R and SA+R groups had significantly better outcomes for postoperative pain control (LA vs. LA+R, p = 0.01; LA vs. SA+R, p = 0.01; SA vs. SA+R, p = 0.01; SA vs. LA+R, p = 0.03) and required less supplemental pain medication. Hospitalization cost was lower and duration shorter in the LA and LA+R groups than in the SA and SA+R groups. There was no significant difference in satisfaction among the four groups. Limitations: This was a single-center retrospective and relatively short-term study. Conclusions: LA+R which could be safely applied in ankle arthroscopy provided satisfactory pain control, reduced postoperative pain intensity, fewer complications, shorter hospital stay, and good cost-effectiveness. It can be safely applied in ankle arthroscopy for the specific patients with ankle osteoarthritis.

Nearly 70% of breast cancers express the estrogen receptor (ER) and are hormone-dependent for cell proliferation and survival. Anti-estrogen therapies with aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) or selective estrogen receptor down regulators (SERDs) are the standard endocrine therapy approach for ER positive breast cancer patients. However, about 30% of patients receiving endocrine therapy will progress during the therapy or become endocrine resistance eventually. The intrinsic or acquired endocrine resistance has become a major obstacle for endocrine therapy. The mechanism of endocrine resistance is very complicated and recently emerging evidence indicates dysregulation of Notch signaling pathway contributes to endocrine resistance in breast cancer patients. The potential mechanisms include regulation of ER, promotion of cancer stem cell (CSC) phenotype and mesenchymal cell ratio, alteration of the local tumor microenvironment and cell cycle. This review will summarize the latest progress on the investigation of Notch signaling pathway in breast cancer endocrine resistance.

Summary: Bivalve mollusks are economically important invertebrates that exhibit marked diversity in benthic lifestyle and provide valuable resources for understanding the molecular basis of adaptation to benthic life. In this report, we present a high-quality, chromosome-anchored reference genome of the Venus clam, Cyclina sinensis. The chromosome-level genome was assembled by Pacific Bioscience single-molecule real-time sequencing, Illumina paired-end sequencing, 10× Genomics, and high-throughput chromosome conformation capture technologies. The final genome assembly of C. sinensis is 903.2 Mb in size, with a contig N50 size of 2.6 Mb and a scaffold N50 size of 46.5 Mb. Enrichment analyses of significantly expanded and positively selected genes suggested evolutionary adaptation of this clam to buried life. In addition, a change in shell color represents another mechanism of adaptation to burial in sediment. The high-quality genome generated in this work provides a valuable resource for investigating the molecular mechanisms of adaptation to buried lifestyle.

Background: The tumor microenvironment (TME) consists of heterogeneous cell populations, including malignant cells and nonmalignant cells that support tumor proliferation, invasion, and metastasis through extensive cross talk. The intra-tumor immune landscape is a critical factor influencing patient survival and response to immunotherapy.Methods: Gene expression data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Immune cell infiltration was determined by single-sample Gene Set Enrichment Analysis (ssGSEA) depending on the integrated immune gene sets from published studies. Univariate analysis was used to determine the prognostic value of the infiltrated immune cells. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen for the most survival-relevant immune cells. An immune-cell characteristic score (ICCS) model was constructed by using multivariate Cox regression analysis.Results: The immune cell infiltration patterns across 32 cancer types were identified, and patients in the high immune cell infiltration cluster had worse overall survival (OS) but better progression-free interval (PFI) compared to the low immune cell infiltration cluster. However, immune cell infiltration showed inconsistent prognostic value depending on the cancer type. High immune cell infiltration (High CI) indicated a worse prognosis in brain lower grade glioma (LGG), glioblastoma multiforme (GBM), and uveal melanoma (UVM), and favorable prognosis in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), sarcoma (SARC), and skin cutaneous melanoma (SKCM). LUAD prognosis was significantly influenced by the infiltration of 13 immune cell types, with high infiltration of all but Type 2 T helper (Th2) cells correlating with a favorable prognosis. The ICCS model based on six most survival-relevant immune cell populations was generated that classified patients into low- and high-ICCS groups with good and poor prognoses, respectively. The multivariate and stratified analyses further revealed that the ICCS was an independent prognostic factor for LUAD.Conclusions: The infiltration of immune cells in 32 cancer types was quantified, and considerable heterogeneity was observed in the prognostic relevance of these cells in different cancer types. An ICCS model was constructed for LUAD with competent prognostic performance, which can further deepen our understanding of the TME of LUAD and can have implications for immunotherapy.

Summary: Dendritic cells (DCs) play a central role in both innate and adaptive immunity. Emerging evidence has demonstrated metabolic reprogramming during DC activation. However, how DC activation is linked with metabolic reprogramming remains unclear. Here we show that pyruvate kinase M2 (PKM2), the rate-limiting enzyme in the last step of glycolysis, is critical for LPS-induced DC activation. Upon DC activation, JNK signaling stimulated p300 association with PKM2 for the acetylation of lysine 433, a classic posttranslational modification critical for PKM2 destabilization and nuclear re-localization. Subsequently, nuclear PKM2 partnered with c-Rel to enhance Il12p35 expression, which is important for Th1 cell differentiation. Meanwhile, decreased enzymatic activity of PKM2 due to detetramerization facilitated glycolysis and fatty acid synthesis, helping DCs meet their need for biomacromolecules. Together, we provide evidence for metabolic control of DC activation and offer insights into aberrant immune responses due to dysregulated Th1 functions.

A 30-year-old woman was admitted to a different hospital with a 2-day history of fever, cough, and expectoration. She had a history of left pulmonary tuberculosis 8 years previously. Chest computed tomography showed an infiltrate in the inferior lobe of the left lung and spot-like calcifications in the anterior lobe of the upper left lobe and lower lobe of the left lung. After antibacterial treatment, the patient’s condition deteriorated and she developed significant pleural effusion on the left side. The pleural effusion assay showed a lymphocyte-predominant exudate with a significantly increased adenosine deaminase level. The patient was transferred to our hospital with a suspected diagnosis of tuberculous pleuritis. A serum test for Mycoplasma pneumoniae -specific immunoglobulin M was positive. Because of the limitations of this test in determining the occurrence of recent infection, a thoracoscopic pleural biopsy was performed, and M. pneumoniae DNA was detected in the biopsy tissue using M. pneumoniae -specific polymerase chain reaction. Thus, the patient was diagnosed with M. pneumoniae -related parapneumonic effusion. Clinicians must be aware of the usefulness and limitations of a high adenosine deaminase level and know that lymphocyte predominance in pleural effusion does not always indicate tuberculous pleurisy, especially in areas of high tuberculosis prevalence.

Zero-dimensional (0D) nanomaterials, including graphene quantum dots (GQDs), carbon quantum dots (CQDs), fullerenes, inorganic quantum dots (QDs), magnetic nanoparticles (MNPs), noble metal nanoparticles, upconversion nanoparticles (UCNPs) and polymer dots (Pdots), have attracted extensive research interest in the field of biosensing in recent years. Benefiting from the ultra-small size, quantum confinement effect, excellent physical and chemical properties and good biocompatibility, 0D nanomaterials have shown great potential in ion detection, biomolecular recognition, disease diagnosis and pathogen detection. Here we first introduce the structures and properties of different 0D nanomaterials. On this basis, recent progress and application examples of 0D nanomaterials in the field of biosensing are discussed. In the last part, we summarize the research status of 0D nanomaterials in the field of biosensing and anticipate the development prospects and future challenges in this field.

Previous studies have shown that cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is frequently inactivated but functions as a tumor suppressor in many solid tumors. However, the characterization of CADM1 expression in ovarian cancer cells and the mechanisms of its tumor suppressor function are not fully understood. We generated ovarian cancer cell lines in which CADM1 was stably upregulated or downregulated. CADM1 expression was significantly decreased in ovarian cancer tissue and cells lines. Functionally, knockdown of CADM1 promoted the growth, migration and invasion of ovarian cancer cells. Conversely, further experimental evidence indicated that overexpression of CADM1 inhibited the migration and invasion of ovarian cancer cells potentially through inhibition of the PI3K/Akt/mTOR signaling pathway by regulating upstream regulators (LXR/RXR, IGF1, IFI44L and C4BPA) and downstream effectors (APP, EDN1, TGFBI and Rap1A). In conclusion, CADM1 inhibits ovarian cancer cell proliferation and migration by potentially regulating the PI3K/Akt/mTOR signaling pathway. CADM1 could be a potential therapeutic target for ovarian cancer.

Exosomes are endosome-derived extracellular vesicles that are released upon the fusion of multivesicular bodies with the plasma membrane. These vesicles contain proteins, lipids, and nucleic acids and are found in various human body fluids. Exosomes can transfer bioactive molecules to nearby or distant recipient cells, thereby affecting their function. Recently, exosomes have gained importance as a medium of communication between tumor cells. An increasing number of studies have found that non-coding RNAs in tumor cell-derived exosomes can regulate tumor microenvironments, inhibit immune cell function, promote the growth and invasion of tumor cells, and impart resistance to chemicals in tumor cells. In this review, we focus on the effects of exosomal long non-coding RNAs (lncRNAs) on tumors. As exosomes and their parent cells have similar biological characteristics and coated lncRNAs can exist stably in vivo without being degraded by RNases, exosomal lncRNAs have emerged as novel non-invasive tumor biomarkers for use in the early diagnosis and evaluation of prognosis of tumors. Advancements in the field have led to the development of a variety of techniques in exosomal non-coding RNA research. Currently, most methods include the separation and purification of exosomes, followed by RNA extraction, reverse transcription, and subsequent analyses; thus, these processes are very tedious and vulnerable to contamination and could lead to inaccurate and inconsistent results. Thus, there has been an increase in the development of detection methods for exosomal RNAs. Here, we discuss the existing research methods, their advantages and disadvantages, and a few new techniques.