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Abstract Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Abstract Background Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. Methods A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. Results There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160–23.190) in non-pCRw/mic group and 5.970 (1.840–19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130–34.090) in non-pCRw/mic group, 9.120 (2.850–29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230–21.500) without statistical significance (p = 0.486). Conclusions Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Abstract Sophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Engineered biosensing bacteria outfitted with such circuits can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiring thyA via horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacterium Bacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.

Cotoneaster densiflorus, a new species of Rosaceae from western Sichuan, China, is described and illustrated. Morphologically, we inferred that the new species belongs to Cotoneaster Ser. Salicifolii sensu Yü et al. (1974) in the Flora of China and Fryer and Hylmö (2009). This species is most similar to C. salicifolius, but differs in its leaf blade of ovate-lanceolate to obovate shape (vs. elliptic-oblong to ovate-lanceolate), smaller length-width ratio of 2.37 ± 0.31 (vs. 3.17 ± 0.32), slightly conduplicate (vs. not conduplicate), less lateral veins of 6–8 pairs (vs. 12–16 pairs), upper surface slightly rugose (vs. rugose), leaf margin plane (vs. revolute), lower surface densely grey tomentose (vs. grey tomentose, with bloom), greater corolla diameter of 7–9 mm (vs. 5–6 mm), styles 2 (vs. 2–3), pyrenes 2 (vs. 2–3), larger pollen grains P/E values of 2.05 ± 0.12 (vs. 1.19 ± 0.05) and leaf epidermis type W (vs. type I). Based on phylogenetic analysis of the whole chloroplast genome, C. densiflorus is sister to C. rhytidophyllus, but distantly related to C. salicifolius.

Abstract Submarine volcanos are the most active areas in the deep sea, but the environmental consequences of frequent volcanic activity on the geophysical fields and biogeochemical processes near hydrothermal chimneys have not been fully understood yet. In particular, how continuous high‐flux thermal energy, the most typical form of energy in active submarine volcanic systems, affects electron transport and geoelectric field remains unknown. This study provides the first evidence that thermal energy can be efficiently converted to electrical energy at an extremely small spatial scale of the submarine black chimneys. The Seebeck coefficient of sulfide chimneys can reach more than 200 μV/K, with high electrical conductivity of 104 S/m and low thermal conductivity of 1.0 W/(m·K) within 300–700 K. A maximal potential gradient of 300 mV/cm under a temperature difference of 300–700 K can be generated by the thermoelectric conversion of sulfide chimneys, with a maximum energy converting efficiency up to 1%. The thermoelectric conversion effect of a global‐scale submarine volcanos could enable electroactive bacteria to fix appromaxiately 105–106 tons of carbon per year. In addition, the thermal‐electrochemical experiments indicated sulfides underwent rapid oxidation under thermoelectric effects, which may help explain the intense oxidative weathering of sulfides in some anoxic deep‐sea hydrothermal zones.

There is growing evidence that the amplitude of low-frequency fluctuation (ALFF) changes in breast cancer patients after chemotherapy. However, longitudinal changes in ALFF during chemotherapy are unclear. To assess the trajectory of ALFF changes during chemotherapy, 36 breast cancer patients underwent both resting-state functional magnetic resonance imaging and neuropsychological testing at three time points, including before neoadjuvant chemotherapy (NAC) (time point 0, TP0), after one cycle of NAC (before the second cycle of NAC, TP1), and upon completion of NAC (pre-operation, TP2). Healthy controls (HC) received the same assessments at matching time points. We compared the longitudinal changes of ALFF in the NAC and two HC groups. In the NAC group, compared with TP0, ALFF values in the right orbital part of the inferior frontal gyrus, left medial orbital part of the superior frontal gyrus, right insula, left medial part of the superior frontal gyrus, and right middle frontal gyrus declined significantly at TP1 and TP2. Compared with TP1, there were no significant changes in ALFF values at TP2. In the two HC groups, there were no significant changes in ALFF at corresponding intervals. We concluded that for breast cancer patients receiving NAC, ALFF values declined significantly in some brain regions after one cycle of NAC and then remained stable until the completion of NAC, and most of the brain regions with ALFF changes were located in the frontal lobe.

This study aims to investigate the effect of limestone filler, sulfate concentration and temperature on the thaumasite sulfate attack (TSA) in Portland cement (PC)-calcium aluminate cement (CAC)-gypsum ternary system. The compressive strength of mortar was tested, while X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were used to analyze the deteriorated products. The results indicate that the ternary system with limestone filler is susceptible to TSA. The higher the limestone content, the higher the TSA is in systems with MgSO4 solution of less than 5%. When the limestone filler content is 10% or 20%, the sulfate attack is mainly presented as gypsum sulfate attack. When the concentration of MgSO4 solution increases, the corrosion is diminished. The ternary system exposed to low concentration MgSO4 solution of 5% is prone to form thaumasite. The lower the temperature, the more vulnerable the system is to TSA. The mortar at 5 °C under 5% MgSO4 solution is rarely damaged and thaumasite could easily be detected.

The antifungal activity and mechanism of rosemary essential oil against Colletotrichum gloeosporioides, the walnut anthracnose pathogen, were investigated using scanning electron microscopy (SEM), index determination and transcriptome technique. The results showed that rosemary essential oil could inhibit the growth of C. gloeosporioides with minimum inhibitory (MIC) and fungicidal (MFC) concentrations of 15.625 μL/mL and 31.25 μL/mL, respectively. Scanning electron microscopy revealed that the mycelium morphology became shriveled, twisted, and severely deformed after being treated with rosemary essential oil. The activity of chitinase, which decomposes fungal cell wall components in C. gloeosporioides, increased. The ergosterol content in the plasma membrane decreased, while the cell contents including nucleic acids, soluble protein and soluble reducing sugar were released resulting in the extracellular electrical conductivity being changed. For metabolic activity, the enzymes succinate dehydrogenase (SDH), malate dehydrogenase (MDH), ATPase and ATP decreased, whereas phosphofructokinase (PFK) increased. Transcriptome sequencing results showed that the antifungal mechanism of rosemary essential oil involves the destruction of the cell wall and membrane, inhibition of genetic material synthesis, and cell division and differentiation. The results are helpful to understand the efficacy and antifungal mechanism of rosemary essential oil against C. gloeosporioides and provide a theoretical basis for the development of rosemary essential oil as a biological control agent.

Precise and scalable regulation of gene expression in mammalian cells is challenging. Here, the authors created a highly tunable CRISPR-based synthetic transcription system for programmable control of mammalian gene expression and cellular activity.

Abstract Polysaccharides from the rhizome of Polygonatum sibiricum display a variety of biological activities, including the regulation of intestinal microbiota, but the polysaccharides from the leaves of P. sibiricum have not been studied extensively. Here, we extracted crude polysaccharides from the leaves of P. sibiricum and further separated and purified them to study the effects of P. sibiricum polysaccharides (PsPs) on intestinal microbes and short-chain fatty acids (SCFAs). The PsPs had a total sugar content of 97.48% and a monosaccharide composition comprising mannose, rhamnose, galacturonic acid, glucose, xylose, and arabinose, with molar ratios of 6.6:15.4:4.5:8.8:40.7:24, respectively. The effects of PsPs on intestinal microflora in mice were also studied, with 16S sequencing results showing an increase in the relative abundance of Firmicutes and a decrease in Bacteroidetes at the phylum level. The abundance of Lactobacillus increased, while those of Lachnospiraceae and Bacteroides reduced (at the genus level) by PsPs treatment. The composition of microbes changed. Levels of SCFAs in the PsPs group were significantly increased compared with control mice, including acetic acid, propionic acid, and butyric acid. These results suggest that PsPs can act as prebiotics, regulating the intestinal tract probiotics.

Antibiotics are very effective in treating a variety of bacterial infections, while clinical overuse of antibiotics can lead to diseases such as antibiotic-associated diarrhea. Numerous studies have shown that natural polysaccharides can be used as prebiotics to alleviate antibiotic-associated diarrhea (AAD). Poria cocos is a medicinal and edible mushroom widely used for thousands of years in China, and our former study demonstrated that water-insoluble polysaccharide (PCY) has the potential prebiotic function. Therefore, we simulated the digestion and fermentation of PCY using feces from volunteers, and then administered it to C57BL/6 mice with AAD to study its effects on the gut microbiota and metabolites. The results indicated that PCY effectively alleviated the symptoms of AAD in mice, restored the intestinal barrier function, improved the content of short-chain fatty acids (SCFAs), decreased the level of inflammatory cytokines, and changed the structure of gut microbiota by increasing the relative abundance of norank_f__Muribaculaceae and unclassified_f__Lachnospiraceae, and decreasing that of Escherichia-Shigella, Staphylococcus and Acinetobacter. This study further demonstrated that PCY is an effective functional prebiotic for improving AAD disease, and provided a new avenue and insight for developing PCY as a functional food or prebiotic for alleviating gastrointestinal diseases.

Abstract Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

Wolfiporia cocos (F. A. Wolf) Ryvarden & Gilb, also known as Poria cocos is an ancient edible and medicinal mushroom that has been valued for thousands of years for its tranquilizing, diuretic, and spleen-enhancing properties. Because of the mushroom’s complex composition, its pharmacological effects have not been fully clarified. Therefore, to expand our knowledge of these effects from a pharmacological perspective and exploit potential medicinal value of fungal mushroom, we extracted three main metabolites from P. cocos, including water-soluble polysaccharides (PCX), water-insoluble polysaccharides (PCY), and triterpenoid saponins (PCZ) for intragastric injection into mice. These injections were made to explore the component’s effects on the mice’s gut microbiota and their metabolomics. The microbiota analysis showed that PCY had the strongest effect on regulating gut microbiota through altering its composition and increasing the number of Lactobacillus (p < 0.01). A total of 1,828 metabolites were detected using metabolomics methods, and the results showed that the three main active metabolites of P. cocos significantly changed the content of short-chain peptides in intestinal metabolites. In conclusion, our study further investigated the pharmacological functions of P. cocos, and revealed the differing effects of its three main metabolites on gut microbiota. The results suggested that PCY is a prominent prebiotic, and provided us with new insights into the potential development of fungal polysaccharides in Chinese traditional medicine.

Angelica dahurica is an ancient herbaceous plant and a famous traditional Chinese medicine. A. dahurica polysaccharides (AdPs) are macromolecular bioactive carbohydrates that have many functions. The animal gut contains a remarkable abundance of microbes that are closely related and play a major role in maintaining the overall health. The intestinal flora is also known as the ‘second genome’ of the human body. To study the functional interactions between AdPs and gut microbiota, we extracted AdPs using water extraction. After a series of treatments, including degreasing, alcohol precipitation, protein decolorization and purification by cellulose column, 200 mg/kg of purified AdPs were administered daily to 5 weeks old Kunming (KM) mice for 21 days. Microbial composition was evaluated in fecal samples using high-throughput sequencing. Our results revealed that AdPs affected the composition and structure of gut microbiota and can potentially regulate the intestinal flora as prebiotics.

To reveal the effects of different land-use types on soil enzyme activities, soil samples were collected from 0–10, 10–20 and 20–30 cm soil layers to compare and analyze soil β-glucosidase (BG), urease (URE), protease (PROT) and catalase (CAT) activities in farmland (FL), abandoned land (AL) and three plantation forests: Platycladus orientalis (L.) Franco (PO), Robinia pseudoacacia L. (RP) and Quercus variabilis Bl. (QV) in the rocky mountainous region of North China. The results showed that the soil enzyme activities varied significantly under different land-use types, and the interannual mean values of FL and PO were remarkably higher than those of other land uses in the 0–30 cm soil layer, in which the soil BG and URE activities of FL were 22% and 12% higher than those of AL, and 428% and 179% higher than those of QV, respectively; the soil PROT and CAT activities of PO were 66% and 23% higher than those of AL, and 479% and 113% higher than those of QV, respectively. Soil BG, URE and PROT activities were all higher in June and lower in December, while soil CAT activity was slightly lower in June. The soil enzymatic activities all showed a notable decrease with the depth of the soil layer. Soil BG, URE, PROT and CAT activities were remarkably (p < 0.01) or significantly (p < 0.05) positively correlated with available nitrogen, available phosphorus, available potassium, dissolved organic carbon (DOC), NO3−-N, soil organic carbon, water content, clay and silt volume fraction, and significantly negatively correlated with sand volume fraction. Soil DOC and pH were important factors influencing soil enzymatic activity, implying that changes in soil enzymatic activity under different land-use types may be the result of a combination of temperature, moisture and plant type. In conclusion, PO plantations are conducive to improving the physicochemical and biological properties of soil and enhance soil fertility, which is a reasonable land-use method to achieve sustainable development in the rocky mountainous region of North China.

Phoebe bournei is a rare and endangered plant endemic to China with higher-value uses in essential oil and structural wood production. Its seedlings are prone to death because of its undeveloped system. Paclobutrazol (PBZ) can improve root growth and development in certain plants, but its concentration effect and molecular mechanism remain unclear. Here, we studied the physiological and molecular mechanisms by which PBZ regulates root growth under different treatments. We found that, with moderate concentration treatment (MT), PBZ significantly increased the total root length (69.90%), root surface area (56.35%), and lateral root number (47.17%). IAA content was the highest at MT and was 3.83, 1.86, and 2.47 times greater than the control, low, and high-concentration treatments. In comparison, ABA content was the lowest and reduced by 63.89%, 30.84%, and 44.79%, respectively. The number of upregulated differentially expressed genes (DEGs) induced at MT was more than that of down-regulated DEGs, which enriched 8022 DEGs in response to PBZ treatments. WGCNA showed that PBZ-responsive genes were significantly correlated with plant hormone content and involved in plant hormone signal transduction and MAPK signal pathway-plant pathways, which controls root growth. The hub genes are observably associated with auxin, abscisic acid syntheses, and signaling pathways, such as PINs, ABCBs, TARs, ARFs, LBDs, and PYLs. We constructed a model which showed PBZ treatments mediated the antagonism interaction of IAA and ABA to regulate the root growth in P. bournei. Our result provides new insights and molecular strategies for solving rare plants’ root growth problems.

Purpose: The malignancy rates within the Breast Imaging Reporting and Data System (BI-RADS) category 4a and 4b lesions were examined, and the correlations with the histopathology results were analyzed. In addition, the positive predictive value (PPV) and clinical utility of BIRADS category 4a and 4b lesions for predicting a malignancy were assessed. Methods : : From January 2017 to December 2019, patients with BI-RADS category 4a and 4b lesions on breast ultrasonography (US) who underwent a subsequent core needle biopsy in the authors’ institution were evaluated. The clinical, pathological, and sonographic features were assessed to identify the malignancy rate and pathologic factors predictive of malignancy. The sensitivity, specificity, PPV, and negative predictive value (NPV) were calculated. A Binary logistic regression test was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Results : : The study population included 314 lesions in 275 patients (mean age, 45.3 years; range, 21–78 years). The overall malignancy rate was 9.8% (31 of 314). The malignancy rates among the BI-RADS category 4a and 4b lesions were 9.3% (28 out of 300) and 21.4% (3 out of 14), respectively. Compared to the well-defined margins, ill-defined margins were associated with an increased risk of breast cancer with a corresponding OR (95% CI) of 1.880 (1.304-2.554). The sensitivity, specificity, PPV, and NPV of the C4a and C4b lesions were as follows: 90.3%, 3.9%, 9.4%, and 78.6%, respectively, for C4a lesions and, 9.7%, 96.1%, 21.4%, and 90.6%, respectively, for C4b lesions. Only the equivocal elasticity on ultrasonography was associated with an increased risk of breast cancer with an OR (95% CI) of 2.357 (1.004-5.532). Conclusion : : BI-RADS categories 4a and 4b are useful for predicting malignancy. Nevertheless, further studies will be needed to identify more predictive factors for breast cancer.

Abstract Background In patients diagnosed with ductal carcinoma in situ (DCIS) with needle biopsy before surgery, invasive component (IC) is often found in the postoperative tissue, which results in altered post-surgical care. However, there are no clinically available factors to predict IC, and few MRI studies are available for the detection of IC in DCIS patients. The purpose of this study was to evaluate which risk factors can predict IC preoperatively. Methods Patients with a DCIS diagnosis based on preoperative biopsy, who underwent breast surgery Kangbuk Samsung Hospital between Jan 2005 and June 2018, were retrospectively evaluated. Clinico-pathological and breast MRI factors were compared between DCIS and DCIS with IC in postsurgical specimens. Results Of the 431 patients with a preoperative diagnosis of DCIS, 34 (7.9%) showed IC during the postoperative pathological investigations, and 217 (50.3%) underwent breast MRI. Among MRI-related factors, Mass-like enhancement on MRI was the sole but significant predictor of IC (HR = 0.26, C.I. = 0.07–0.93, p = 0.038), while nipple-areolar complex invasion, enhancement peak and pattern were not statistically significant. Nuclear grade was the only significant predictor of IC in the analysis of other clinico-pathological factors (HR = 2.39, C.I. = 1.05–5.42, p = 0.038 in univariate analysis, HR = 2.86, C.I. = 1.14–7.14, p = 0.025 in multivariate analysis). Conclusions Mass-like enhancement on MRI and high nuclear grade were associated with IC in patients with preoperative diagnosis of DCIS. Considering the high sensitivity of breast MRI for IC, further evaluation of the predictive value of MRI in preoperative DCIS patients is desirable.

Purpose: Upstaging to invasive cancer (IC) is often found after surgery in those patients diagnosed with ductal carcinoma in situ (DCIS) and who underwent preoperative needle biopsy. This may change the post-surgical plans that include the re-operation, chemotherapy, and/or radiotherapy. Yet, there are no clinically available factors to predict IC in preoperatively diagnosed DCIS patients. This study evaluated the clinical and pathological predictive risk factors for upgrading DCIS to IC. Methods: This study retrospectively evaluated those patients who were diagnosed with DCIS preoperatively, and this diagnosis was followed by performing breast surgery between Jan 2005 and June 2018. Clinico-pathological factors were collected for the analysis between the pure DCIS group and the IC group. Results: Of the 431 patients included in the study, 34 (7.9%) were upstaged to IC after surgery, and 397 (92.1%) were diagnosed as having pure DCIS. The nuclear grade was the sole predictor of upstaging to IC on the analysis of the clinico-pathological factors (odds ratio [OR] = 2.39, 95% confidence interval [95% CI] = 1.05–5.42, P = 0.038 on the univariate analysis; aOR = 2.86, 95% CI = 1.14–7.14, P = 0.025 on the multivariate analysis). The mass’s size and characteristics, as determined by sonography, were not predictive of IC. Conclusion: The sonographic findings were not significant factors for predicting IC in preoperative DCIS patients. A high nuclear grade was the only statistically significant factor associated with IC. Considering the variability of the gauge of biopsy needles or the method for needle biopsy, large-scale prospective studies that control these variables may well reveal available predictive factors of IC in patients with DCIS.

ABSTRACT Shigellosis causes most diarrheal deaths worldwide, particularly affecting children. Shigella invades and replicates in the epithelium of the large intestine, eliciting inflammation and tissue destruction. To understand how Shigella rewires macrophages prior to epithelium invasion, we performed genome-wide and focused secondary CRISPR knockout and CRISPR interference (CRISPRi) screens in Shigella flexneri-infected human monocytic THP-1 cells. Knockdown of the Toll-like receptor 1/2 signaling pathway significantly reduced proinflammatory cytokine and chemokine production, enhanced host cell survival, and controlled intracellular pathogen growth. Knockdown of the enzymatic component of the mitochondrial pyruvate dehydrogenase complex enhanced THP-1 cell survival. Small-molecule inhibitors blocking key components of these pathways had similar effects; these were validated with human monocyte-derived macrophages, which closely mimic the in vivo physiological state of macrophages postinfection. High-throughput CRISPR screens can elucidate how S. flexneri triggers inflammation and redirects host pyruvate catabolism for energy acquisition before killing macrophages, pointing to new shigellosis therapies. IMPORTANCE Treatment for shigellosis is becoming increasingly difficult as resistance to antibiotics becomes more prevalent. One way to prevent this significant public health problem from developing into a full-blown crisis is to approach shigellosis intervention from the point of view of the host. So far, little is known about the specific biological pathways that might be modulated in macrophages, sentinel cells of the innate immune system, to strengthen the response to Shigella infection. In this work, we conducted CRISPR screens to comprehensively decipher the complexity of macrophage-Shigella interactions and to discover new potential therapeutic interventions against Shigella flexneri infection. Our work highlights systematic genetic perturbation strategies to provide direct causal evidence showing how intracellular pathogens manipulate innate immune cells.

Cuticular waxes comprise the hydrophobic layer that protects crops against nonstomatal water loss and biotic and abiotic stresses. Expanding on our current knowledge of the genes that are involved in cuticular wax biosynthesis and regulation plays an important role in dissecting the processes of cuticular wax metabolism. In this study, we identified the Cer-GN1 barley (Hordeum vulgare L.) mutant that is generated by ethyl methanesulfonate mutagenesis with a glossy spike phenotype that is controlled by a single recessive nuclear gene. A physiological analysis showed that the total cuticular wax loads of Cer-GN1 were one-third that of the progenitor wild-type (WT), and its water loss rate was significantly accelerated (p < 0.05). In addition, Cer-GN1 was defective in the glume’s cuticle according to the toluidine blue dye test, and it was deficient in the tubule-shaped crystals which were observed on the glume surfaces by scanning electron microscopy. Using metabolomics and transcriptomics, we investigated the impacts of cuticular wax composition and waxy regulatory genes on the loss of the glaucous wax in the spikes of Cer-GN1. Among the differential metabolites, we found that 16-hydroxyhexadecanoic acid, which is one of the predominant C16 and C18 fatty acid-derived cutin monomers, was significantly downregulated in Cer-GN1 when it was compared to that of WT. We identified two novel genes that are located on chromosome 4H and are downregulated in Cer-GN1 (HvMSTRG.29184 and HvMSTRG.29185) that encode long-chain fatty acid omega-monooxygenase CYP704B1, which regulates the conversion of C16 palmitic acid to 16-hydroxyhexadecanoic acid. A quantitative real-time PCR revealed that the expression levels of HvMSTRG.29184 and HvMSTRG.29185 were downregulated at 1, 4, 8, 12, and 16 days after the heading stage in Cer-GN1 when it was compared to those of WT. These results suggested that HvMSTRG.29184 and HvMSTRG.29185 have CYP704B1 activity, which could regulate the conversion of C16 palmitic acid to 16-hydroxyhexadecanoic acid in barley. Their downregulation in Cer-GN1 reduced the synthesis of the cuticular wax components and ultimately caused the loss of the glaucous wax in the spikes. It is necessary to verify whether HvMSTRG.29184 and HvMSTRG.29185 truly encode a CYP704B1 that regulates the conversion of C16 palmitic acid to 16-hydroxyhexadecanoic acid in barley.

Airport pavement concrete often suffers from freeze–thawing damage in high latitude and cold areas. In addition, the use of aircraft deicer makes the airport pavement concrete suffer from salt-freezing damage. To improve the durability of airport pavement concrete, modified polyester synthetic fiber (FC), cellulose fiber (CF), and basalt fiber (BF) reinforced concrete were prepared in this paper. The mechanical strength, pore structure, and frost resistance (freeze–thawing and salt freezing) of fiber-reinforced concrete were investigated. The effects of the combined action of fiber (fiber type and content) and surface treatment methods (spraying silane and impregnating silane) on the frost resistance of concrete were investigated. The results show that the flexural strength of concrete is positively correlated with the elastic modulus of fiber, but has little effect on the compressive strength. Fiber can reduce mass loss and dynamic modulus loss of concrete subjected to frost damage. FC more effectively improved the frost resistance of concrete than CF. After 30 cycles of salt freezing, the spalling amount of concrete sprayed or soaked with silane was decreased by 65.5% and 55.5%, respectively. Adding fiber and impregnating silane reduced the spalled concrete by up to 70.5%. Spraying silane treatment is better than impregnating silane treatment in enhancing the frost resistance of concrete because a better silane condensation reaction is achieved with spraying silane.

Liver injury is a clinical disorder caused by toxins, drugs, and alcohol stimulation without effective therapeutic approaches thus far. Scutellarin (SCU), isolated from the edible herb Erigeron breviscapus (Vant.) Hand. -Mazz. showed potential hepatoprotective effects, but the mechanisms remain unknown. In this study, transcriptomics combined with nontargeted metabolomics and 16S rRNA amplicon sequencing were performed to elucidate the functional mechanisms of SCU in carbon tetrachloride (CCl4)–induced liver injury in mice. The results showed that SCU exerted potential hepatoprotective effects against CCl4-induced liver injury by repressing CYP2E1 and IκBα/NF-κB signaling pathways, modulating the gut microbiota (especially enriching Lactobacillus), and regulating the endogenous metabolites involved in lipid metabolism and bile acid homeostasis. SCU originates from a functional food that appears to be a promising agent to guard against liver injury.

Crowds are playing an increasingly important role in the research and application of geoscience by providing spatial data via crowdsourcing. However, low-public participation and poor quality of data submissions have greatly restricted the application of spatial crowdsourcing (SC) and other similar models, thus garnering the attention of scientists in this field. In this paper, we design a precise incentive mechanism based on a Bayesian game for SC that successfully avoids the conditions limited by the Gibbard-Satterthwaite impossibility theorem. Under this mechanism, the outsourcer carries out a Bayesian game with the participants under the circumstance of incomplete information by setting a certain amount of reference information that is not visible to the participants. Participants gain far more utility by telling the truth than that of they gain by lying and thus have a stronger motivation to submit higher-quality data. In implementing this mechanism to automatically compute the actual utility of participants and integrate data results, we propose a geometric primitive matching algorithm based on the Jaccard coefficient. Through both rigorous theoretical analyses and real experiments, the incentive mechanism that we propose is incentive-compatible and can greatly improve data quality.

The impact of ponds by urbanization has been widely discussed on the landscape scale. However, relatively few studies have explored the spatial differentiation of pond landscapes across urban-rural gradients in rapidly urbanising areas. In this study, we applied the DeepLabv3+ network to perform a semantic segmentation on Google Map images to extract ponds in the Pearl River Delta (PRD) region, China; then we employed geographic information systems to analyse the ponds changes in 665 towns along an urban-rural gradient in the PRD. Results indicate that there are clear differences in landscapes between the urban core, urban, peri-urban, agricultural, and forested zone in terms of pond area and size. In total, 57.84% and 31.33% of the ponds are distributed in the peri-urban and agricultural zone, respectively; fewer ponds are present at either end of the urban-rural gradient. Owing to the legacy effects of historical land use and river systems, urban and peri-urban zone in the central and western parts of the PRD are still rich in ponds. We propose that management measures should be implemented according to the characteristics of different pond landscapes.

The Zhunsujihua porphyry Mo-Cu deposit is located in the Erenhot–East Ujimqin metallogenic belt in northeastern China. Granodioritic intrusions in the mining area are dominated by granodiorite and granodiorite porphyry, but the Mo mineralization is limited within the granodiorite. Zircon LA-ICP-MS U-Pb dating yields crystallization ages of 301.5 ± 3.0 Ma for granodiorite and 296.0 ± 3.0 Ma for granodiorite porphyry. These ages constrain the magmatic activity at the Zhunsujihua deposit that took place during the subduction of the Paleo-Asian oceanic plate. Whole-rock geochemical data suggest that the granodioritic intrusions belong to calc-alkaline and high-K calc-alkaline series, and are characterized by enrichment in K, Rb, U, Th, and Pb, and depletion in Nb, Ta, Ti, and P. The negative Eu, Ba, and Sr anomalies suggest that they have experienced extensive fractionation of plagioclase. Trace element compositions of zircons from the Zhunsujihua deposit provide constraints on the oxygen fugacity (ƒO2) of the magma, which is shown to high values with ∆FMQ = +0.5 to +5.6. The wide range of zircon εHf (t) (+1.3~+9.4) values, positive whole-rock εNd (t) (+2.5~+3.9) values, and relatively low initial (87Sr/86Sr)i (0.70367~0.70561) ratios indicate that the magmas mainly originated from a juvenile lower crust source derived from depleted mantle, but mixed with pre-existing crustal components. Moreover, the juvenile lower crust represents the main source of Mo for the Zhunsujihua deposit. A high magmatic oxygen fugacity and fractional crystallization played key roles in forming the Zhunsujihua deposit.

Abstract Background Carcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer. Methods Invasive ductal breast cancer patients (N = 145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures. Results CD8 + TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73–12.31) was associated with poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR p for trend = 0.063). Conclusions A relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.

Edible plant oil (EPO) is an indispensable nutritional resource for human health. Various cultivars of oil-bearing plants are grown worldwide, and the chemical compositions of different plant oils are diverse. The extremely complex components in oils lead to diverse standards for evaluating the quality and safety of different EPOs. The environment poses great challenges to the EPO safety and quality during the entire industrial chain, including plant cultivation, harvesting, oil processing, and storage. Environmental risk factors include heavy metal or pesticide residue pollution, insect or harmful microbial infestation, and rancidity. Here, the diverse components in oil and various oil-producing processes are discussed, including plant species, oil yield, and composition complexity, environmental factors that degrade oil quality. Additionally, we propose a whole-industrial-chain monitoring system instead of current single-link-monitoring approach by monitoring and tracking the quality and safety of EPOs during the entire process of plant cultivation, raw materials harvest, oil process, and EPOs storage. This will provide guidance for monitoring the quality and safety of EPOs, which were challenged by the deteriorating environment.

Cinnamomum camphora is an evergreen tree native to China and distributed to some Asian countries. Its leaves are rich in bioactive compounds and their pharmacological effects are well-known. A potent method to extract and preserve the active biological substances is crucial for latter application in bioenergy and as chemical raw material. In this study, the metabolite profiles of C. camphora were comprehensively analyzed by using FT-IR and GC-MS after extracted by three type of solvent: ethanol, benzene, and acetone. The identified chemical compounds were then classified into different functional groups based on previous study. Our result proposes the potential application of C. camphora into biomedicine, bioenergy, and chemical raw materials industry.

In the paper, the method of deicing and melting snow by the carbon fiber heating wire (CFHW) embedded in the airport asphalt pavement is proposed to improve the security of airport operation. The field experiment of deicing and melting snow on the airport asphalt pavement is conducted. Deicing and melting snow, asphalt pavement temperature, ice-free area ratio, and snow-free area ratio are analyzed. Electrical power with 350 W/m2 is input to the airport asphalt pavement for deicing and melting snow by the CFHW. In the experiment, 3 mm ice can be melted, and the average infrared ray temperature (IRT) of the airport asphalt pavement surface can achieve an increment of 13.0°C in 2.5 hours when the air temperature is from −7.5°C to −2.2°C. Snow with 3.2 mm precipitation can be melted in 2 hours when the air temperature is from −4.8°C to −3.5°C, and the asphalt pavement temperature can achieve an increment of 5.9°C at the depth of 0.5 cm. The results show that the method of deicing and melting snow on the airport asphalt pavement by the CFHW is practicable in the cold zone.

The deterioration of Portland cement pervious concrete (PCPC) subjected to wet-dry cycles in the simulated acid rain solution was investigated; 4% silica fume (SF) and 8% fine aggregate (FAG) were used to replace part of cement and the coarse aggregates (weight by weight), respectively. The wear resistance, the compressive, and flexural strength of PCPC were measured. The results show that after 12 wet-dry cycles in acid rain solution the compressive strength and the flexural strength of control PCPC are decreased by 30.7% and 40.8%. The final compressive strength of PCPC with 4% SF and PCPC with 8% FAG is increased by 6.9% and 30.3%, and the final flexural strength is increased by 25.4% and 72.3%, respectively. The wear loss of PCPC is decreased by 58.8% and 81.9% when 4% SF and 8% FAG is added to PCPC, respectively. The microstructures of PCPC with wet-dry cycles are also discussed.

Abstract Background Pseudomonas aeruginosa ATCC 27853 was isolated from a hospital blood specimen in 1971 and has been widely used as a model strain to survey antibiotics susceptibilities, biofilm development, and metabolic activities of Pseudomonas spp.. Although four draft genomes of P. aeruginosa ATCC 27853 have been sequenced, the complete genome of this strain is still lacking, hindering a comprehensive understanding of its physiology and functional genome. Results Here we sequenced and assembled the complete genome of P. aeruginosa ATCC 27853 using the Pacific Biosciences SMRT (PacBio) technology and Illumina sequencing platform. We found that accessory genes of ATCC 27853 including prophages and genomic islands (GIs) mainly contribute to the difference between P. aeruginosa ATCC 27853 and other P. aeruginosa strains. Seven prophages were identified within the genome of P. aeruginosa ATCC 27853. Of the predicted 25 GIs, three contain genes that encode monoxoygenases, dioxygenases and hydrolases that could be involved in the metabolism of aromatic compounds. Surveying virulence-related genes revealed that a series of genes that encode the B-band O-antigen of LPS are lacking in ATCC 27853. Distinctive SNPs in genes of cellular adhesion proteins such as type IV pili and flagella biosynthesis were also observed in this strain. Colony morphology analysis confirmed an enhanced biofilm formation capability of ATCC 27853 on solid agar surface compared to Pseudomonas aeruginosa PAO1. We then performed transcriptome analysis of ATCC 27853 and PAO1 using RNA-seq and compared the expression of orthologous genes to understand the functional genome and the genomic details underlying the distinctive colony morphogenesis. These analyses revealed an increased expression of genes involved in cellular adhesion and biofilm maturation such as type IV pili, exopolysaccharide and electron transport chain components in ATCC 27853 compared with PAO1. In addition, distinctive expression profiles of the virulence genes lecA, lasB, quorum sensing regulators LasI/R, and the type I, III and VI secretion systems were observed in the two strains. Conclusions The complete genome sequence of P. aeruginosa ATCC 27853 reveals the comprehensive genetic background of the strain, and provides genetic basis for several interesting findings about the functions of surface associated proteins, prophages, and genomic islands. Comparative transcriptome analysis of P. aeruginosa ATCC 27853 and PAO1 revealed several classes of differentially expressed genes in the two strains, underlying the genetic and molecular details of several known and yet to be explored morphological and physiological potentials of P. aeruginosa ATCC 27853.

The minimum weight vertex independent dominating set (MWVIDS) problem is an important version of the minimum independent dominating set. The MWVIDS problem has a number of applications in many fields. However, the MWVIDS problem is known to be NP-hard and thus computationally challenging. In this work, we present the improved memetic algorithm called MSSAS for solving the MWVIDS problem. The proposed MSSAS algorithm combines probability-based dynamic optimization (PDO) (to generate good and diverse offspring solutions by assembling elements of existing good solutions) as well as a local search phase named C_LS (to seek high-quality local optima by combining the idea of constrained-based two-level configuration checking strategy and tabu mechanism). The extensive results on popular DIMACS and BHOLIB benchmarks demonstrate that MSSAS competes favorably with the state-of-the-art algorithms. In addition, we analyze the benefits of the newly raised components including two above proposed ideas with our memetic framework. It is worth mentioning that the combination of both components has excellent effects for the MWVIDS problem.

The interrelationship between menopausal stage, excessive adiposity and dense breasts remains unclear. We aimed to investigate the relationship between menopausal stage and dense-breast prevalence in midlife women while considering a possible effect modification of being overweight. The present cross-sectional study comprised 82,677 Korean women, aged 35–65 years, who attended a screening exam. Menopausal stages were categorized based on the Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Mammographic breast density was categorized according to Breast Imaging Reporting and Data System (BI-RADS). Dense breasts were defined as BI-RADS Breast Density category D (extremely dense). The prevalence of dense breasts decreased as menopausal stage increased (p-trend < 0.001), and this pattern was pronounced in overweight women than non-overweight women (p-interaction = 0.016). Compared with pre-menopause, the multivariable-adjusted prevalence ratios (and 95% confidence intervals) for dense breasts were 0.98 (0.96–1.00) in early transition, 0.89 (0.86–0.92) in late transition, and 0.55 (0.52–0.59) in post-menopause, among non-overweight women, while corresponding prevalence ratios were 0.92 (0.87–0.98), 0.83 (0.77–0.90) and 0.36 (0.31–0.41) among overweight women. The prevalence of dense breasts was inversely associated with increasing menopausal stages and significantly decreased from the late menopausal transition, with stronger declines among overweight women.

Hulless barley (Hordeum vulgare L. var. nudum) is one of the most important crops in the Qinghai-Tibet Plateau. Soil salinity seriously affects its cultivation. To investigate the mechanism of salt stress response during seed germination, two contrasting hulless barley genotypes were selected to first investigate the molecular mechanism of seed salinity response during the germination stage using RNA-sequencing and isobaric tags for relative and absolute quantitation technologies. Compared to the salt-sensitive landrace lk621, the salt-tolerant one lk573 germinated normally under salt stress. The changes in hormone contents also differed between lk621 and lk573. In lk573, 1597 differentially expressed genes (DEGs) and 171 differentially expressed proteins (DEPs) were specifically detected at 4 h after salt stress, and correspondingly, 2748 and 328 specifically detected at 16 h. Most specific DEGs in lk573 were involved in response to oxidative stress, biosynthetic process, protein localization, and vesicle-mediated transport, and most specific DEPs were assigned to an oxidation-reduction process, carbohydrate metabolic process, and protein phosphorylation. There were 96 genes specifically differentially expressed at both transcriptomic and proteomic levels in lk573. These results revealed the molecular mechanism of salt tolerance and provided candidate genes for further study and salt-tolerant improvement in hulless barley.

As breast cancer is the leading cause of cancer-related deaths in women population worldwide, ongoing endeavor has been made for alternative regimens with improved efficacy but fewer adverse effects. Recently, active components from the spores of Ganoderma lucidum have attracted much attention for their versatile biological activities owing to the advance in sporoderm-breaking technology. Here, anticancer potential of an extract derived from the sporoderm-breaking spores of G. lucidum (ESG) was explored in a 4T1-breast cancer xenograft mice model. Results showed that ESG was able to suppress 4T1 tumor growth in vivo rather than in vitro. Flowcytometry analysis revealed that ESG could significantly increase both cytotoxic T cell (Tc) population and the ratio of Tc to helper T cell (Th) in peripheral blood of the tumor-bearing mouse; similar promotion on Tc was also found in tumor-infiltrating lymphocyte. Moreover, ESG evidently downregulated the two immune checkpoints, programmed cell death protein-1 (PD-1, in the spleen) and cytotoxic T lymphocyte antigen-4 (CTLA-4, in the tumor), suggesting that ESG could effectively restore the T cell paradigm by recovering the exhaustion status via suppressing the co-inhibitory checkpoints. By 16S rRNA gene sequence analysis on the fecal microbiota, it was found that ESG would remodeling the overall structure of the samples from tumor-bearing mice toward that of the normal counterparts, including 18 genera in 5 phyla, together with regulations on several genes that are responsible for signaling pathways involved in metabolism, cellular processes, and environmental information processing. Collectively, this study demonstrated that ESG would serve as a natural anticancer adjuvant via a restoration on the exhausted Tc, highlighting important clinical implications for the treatment of breast cancer.

A lack of phosphorus (P) in plants can severely constrain growth and development. Barley, one of the earliest domesticated crops, is extensively planted in poor soil around the world. To date, the molecular mechanisms of enduring low phosphorus, at the transcriptional level, in barley are still unclear. In the present study, two different barley genotypes (GN121 and GN42)—with contrasting phosphorus efficiency—were used to reveal adaptations to low phosphorus stress, at three time points, at the morphological, physiological, biochemical, and transcriptome level. GN121 growth was less affected by phosphorus starvation and recovery than that of GN42. The biomass and inorganic phosphorus concentration of GN121 and GN42 declined under the low phosphorus-induced stress and increased after recovery with normal phosphorus. However, the range of these parameters was higher in GN42 than in GN121. Subsequently, a more complete genome annotation was obtained by correcting with the data sequenced on Illumina HiSeq X 10 and PacBio RSII SMRT platform. A total of 6,182 and 5,270 differentially expressed genes (DEGs) were identified in GN121 and GN42, respectively. The majority of these DEGs were involved in phosphorus metabolism such as phospholipid degradation, hydrolysis of phosphoric enzymes, sucrose synthesis, phosphorylation/dephosphorylation and post-transcriptional regulation; expression of these genes was significantly different between GN121 and GN42. Specifically, six and seven DEGs were annotated as phosphorus transporters in roots and leaves, respectively. Furthermore, a putative model was constructed relying on key metabolic pathways related to phosphorus to illustrate the higher phosphorus efficiency of GN121 compared to GN42 under low phosphorus conditions. Results from this study provide a multi-transcriptome database and candidate genes for further study on phosphorus use efficiency (PUE).

Brachyury has been characterized as a driver of epithelial–mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no response = 2.6, partial response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant ( p = 0.62). We also observed a significant association between forkhead box protein 3 ( p = 0.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.

The Haisugou porphyry Mo deposit is located in the northern Xilamulun district, northeastern China. Based on alteration and mineralization styles and crosscutting relationships, the hydrothermal evolution in Haisugou can be divided into three stages: an early potassic alteration stage with no significant metal deposition, a synmineralization sericite-chlorite alteration stage with extensive Mo precipitation, and a postmineralization stage characterized by barren quartz and minor calcite and fluorite. The coexistence of high-salinity brine inclusions with low-salinity inclusions both in potassic alteration stage (~440°C) and locally in the early time of mineralization stage (380–320°C) indicates the occurrence of fluid boiling. The positive correlations between the homogenization temperatures and the salinities of the fluids and the low oxygen isotopic compositions (δ18Ofluid < 3‰) of the syn- to postmineralization quartz together suggest the mixing of magmatic fluids with meteoric water, which dominated the whole mineralization process. The early boiling fluids were not responsible for ore precipitation, whereas the mixing with meteoric water, which resulted in temperature decrease and dilution that significantly reduced the metal solubility, should have played the major role in Mo mineralization. Combined fluid inclusion microthermometry and chlorite geothermometer results reveal that ore deposition mainly occurred between 350 and 290°C in Haisugou.

Non-targeted analysis (NTA) using high-resolution mass spectrometry allows scientists to detect and identify a broad range of compounds in diverse matrices for monitoring exposure and toxicological evaluation without a priori chemical knowledge. NTA methods present an opportunity to describe the constituents of a sample across a multidimensional swath of chemical properties, referred to as "chemical space." Understanding and communicating which region of chemical space is extractable and detectable by an NTA workflow, however, remains challenging and non-standardized. For example, many sample processing and data analysis steps influence the types of chemicals that can be detected and identified. Accordingly, it is challenging to assess whether analyte non-detection in an NTA study indicates true absence in a sample (above a detection limit) or is a false negative driven by workflow limitations. Here, we describe the need for accessible approaches that enable chemical space mapping in NTA studies, propose a tool to address this need, and highlight the different ways in which it could be implemented in NTA workflows. We identify a suite of existing predictive and analytical tools that can be used in combination to generate scores that describe the likelihood a compound will be detected and identified by a given NTA workflow based on the predicted chemical space of that workflow. Higher scores correspond to a higher likelihood of compound detection and identification in a given workflow (based on sample extraction, data acquisition, and data analysis parameters). Lower scores indicate a lower probability of detection, even if the compound is truly present in the samples of interest. Understanding the constraints of NTA workflows can be useful for stakeholders when results from NTA studies are used in real-world applications and for NTA researchers working to improve their workflow performance. The hypothetical ChemSpaceTool suggested herein could be used in both a prospective and retrospective sense. Prospectively, the tool can be used to further curate screening libraries and set identification thresholds. Retrospectively, false detections can be filtered by the plausibility of the compound identification by the selected NTA method, increasing the confidence of unknown identifications. Lastly, this work highlights the chemometric needs to make such a tool robust and usable across a wide range of NTA disciplines and invites others who are working on various models to participate in the development of the ChemSpaceTool. Ultimately, the development of a chemical space mapping tool strives to enable further standardization of NTA by improving method transparency and communication around false detection rates, thus allowing for more direct method comparisons between studies and improved reproducibility. This, in turn, is expected to promote further widespread applications of NTA beyond research-oriented settings.

Introduction. Several studies have shown the feasibility and safety of both transperitoneal and posterior retroperitoneal approaches for single incision laparoscopic adrenalectomy, but none have compared the outcomes according to the left- or right-sided location of the adrenal glands. Materials and Methods. From 2009 to 2013, 89 patients who received LAMP (laparoscopic adrenalectomy through mono port) were analyzed. The surgical outcomes attained using the transperitoneal approach (TPA) and posterior retroperitoneal approach (PRA) were analyzed and compared. Results and Discussion. On the right side, no significant differences were found between the LAMP-TPA and LAMP-PRA groups in terms of patient characteristics and clinicopathological data. However, outcomes differed in which LAMP-PRA group had a statistically significant shorter mean operative time (84.13 ± 41.47 min versus 116.84 ± 33.17 min; P=0.038), time of first oral intake (1.00 ± 0.00 days versus 1.21 ± 0.42 days; P=0.042), and length of hospitalization (2.17 ± 0.389 days versus 3.68 ± 1.38 days; P≤0.001), whereas in left-sided adrenalectomies LAMP-TPA had a statistically significant shorter mean operative time (83.85 ± 27.72 min versus 110.95 ± 29.31 min; P=0.002). Conclusions. We report that LAMP-PRA is more appropriate for right-sided laparoscopic adrenalectomies due to anatomical characteristics and better surgical outcomes. For left-sided laparoscopic adrenalectomies, however, we propose LAMP-TPA as a more suitable method.