CT-based radiomics for predicting lymph node metastasis in esophageal cancer: a systematic review and meta-analysis.

Objective: We aimed to evaluate the diagnostic effectiveness of computed tomography (CT)-based radiomics for predicting lymph node metastasis (LNM) in patients diagnosed with esophageal cancer (EC). Methods: The present study conducted a comprehensive search by accessing the following databases: PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying relevant studies published until July 10th, 2023. The diagnostic accuracy was summarized using the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). The researchers utilized Spearman's correlation coefficient for assessing the threshold effect, besides performing meta-regression and subgroup analysis for the exploration of possible heterogeneity sources. The quality assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies-2 and the Radiomics Quality Score (RQS). Results: The meta-analysis included six studies conducted from 2018 to 2022, with 483 patients enrolled and LNM rates ranging from 27.2% to 59.4%. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC, along with their corresponding 95% CI, were 0.73 (0.67, 0.79), 0.76 (0.69, 0.83), 3.1 (2.3, 4.2), 0.35 (0.28, 0.44), 9 (6, 14), and 0.78 (0.74, 0.81), respectively. The results demonstrated the absence of significant heterogeneity in sensitivity, while significant heterogeneity was observed in specificity; no threshold effect was detected. The observed heterogeneity in the specificity was attributed to the sample size and CT-scan phases (P < 0.05). The included studies exhibited suboptimal quality, with RQS ranging from 14 to 16 out of 36. However, most of the enrolled studies exhibited a low-risk bias and minimal concerns relating to applicability. Conclusion: The present meta-analysis indicated that CT-based radiomics demonstrated a favorable diagnostic performance in predicting LNM in EC. Nevertheless, additional high-quality, large-scale, and multicenter trials are warranted to corroborate these findings. Systematic Review Registration: Open Science Framework platform at https://osf.io/5zcnd.

Elucidation of sterol biosynthesis pathway and its co-regulation with fatty acid biosynthesis in the oleaginous marine protist Schizochytrium sp.

Sterols constitute vital structural and regulatory components of eukaryotic cells. In the oleaginous microorganism Schizochytrium sp. S31, the sterol biosynthetic pathway primarily produces cholesterol, stigmasterol, lanosterol, and cycloartenol. However, the sterol biosynthesis pathway and its functional roles in Schizochytrium remain unidentified. Through Schizochytrium genomic data mining and a chemical biology approach, we first in silico elucidated the mevalonate and sterol biosynthesis pathways of Schizochytrium. The results showed that owing to the lack of plastids in Schizochytrium, it is likely to use the mevalonate pathway as the terpenoid backbone pathway to supply isopentenyl diphosphate for the synthesis of sterols, similar to that in fungi and animals. In addition, our analysis revealed a chimeric organization of the Schizochytrium sterol biosynthesis pathway, which possesses features of both algae and animal pathways. Temporal tracking of sterol profiles reveals that sterols play important roles in Schizochytrium growth, carotenoid synthesis, and fatty acid synthesis. Furthermore, the dynamics of fatty acid and transcription levels of genes involved in fatty acid upon chemical inhibitor-induced sterol inhibition reveal possible co-regulation of sterol synthesis and fatty acid synthesis, as the inhibition of sterol synthesis could promote the accumulation of fatty acid in Schizochytrium. Sterol and carotenoid metabolisms are also found possibly co-regulated, as the inhibition of sterols led to decreased carotenoid synthesis through down-regulating the gene HMGR and crtIBY in Schizochytrium. Together, elucidation of the Schizochytrium sterol biosynthesis pathway and its co-regulation with fatty acid synthesis lay the essential foundation for engineering Schizochytrium for the sustainable production of lipids and high-value chemicals.

Rewiring the Metabolic Network to Increase Docosahexaenoic Acid Productivity in Crypthecodinium cohnii by Fermentation Supernatant-Based Adaptive Laboratory Evolution.

Docosahexaenoic acid (DHA, 22:6n-3) plays significant roles in enhancing human health and preventing human diseases. The heterotrophic marine dinoflagellate Crypthecodinium cohnii is a good candidate to produce high-quality DHA. To overcome the inhibition caused by the fermentation supernatant in the late fermentation stage of DHA-producing C. cohnii, fermentation supernatant-based adaptive laboratory evolution (FS-ALE) was conducted. The cell growth and DHA productivity of the evolved strain (FS280) obtained after 280 adaptive cycles corresponding to 840 days of evolution were increased by 161.87 and 311.23%, respectively, at 72 h under stress conditions and increased by 19.87 and 51.79% without any stress compared with the starting strain, demonstrating the effectiveness of FS-ALE. In addition, a comparative proteomic analysis identified 11,106 proteins and 910 differentially expressed proteins, including six stress-responsive proteins, as well as the up- and downregulated pathways in FS280 that might contribute to its improved cell growth and DHA accumulation. Our study demonstrated that FS-ALE could be a valuable solution to relieve the inhibition of the fermentation supernatant at the late stage of normal fermentation of heterotrophic microalgae.

Construction of MoS2/Mxene heterostructure on stress-modulated kapok fiber for high-rate sodium-ion batteries.

Molybdenum disulfide (MoS2) has possession of a layered structure and high theoretical capacity, which is a candidate anode material for sodium ion batteries. However, unmodified MoS2 are inflicted with a poor cycling stability and an inferior rate capability upon charge/discharge processes. Considering that the shape and size of anode materials play a key role in the performance of anode materials, this paper proposes a multi-level composite structure formed by the micro-nano materials based on self-assembled molybdenum disulfide (MoS2) nanoflowers, Mxene and hollow carbonized kapok fiber (CKF). The micro-nano materials can be connected to form heterojunction and agglomeration can be avoided. The load bearing of heterostructure and stress release of CKF are coordinated to form a double protection mechanism, which improves the conductivity and structural stability of hybrid materials. Based on the above advantages, it has higher specific capacity than pure MoS2, and has better rate performance (639.3, 409.5, 386.2, 372, 338, 422.8 and 434.7 mAh g-1 at the current density of 0.05, 0.1, 0.2, 0.5, 1 ,0.1 and 0.05 A·g-1, respectively). The stress-modulated strategies can provide new insights for the design and construction of transition metal sulfides heterostructures to achieve high performance sodium ion batteries.

Carbon nitride/positive carbon black anchoring PtNPs assembled byγ-rays as ORR catalyst with excellent stability.

Electrocatalytic performance of low-cost graphitic carbon nitride (CN) is greatly limited by its limited conductivity and small specific surface area. Herein, a simple and cost-effective idea to produce novel nanocomposite is constructed by the CN and cetyl trimethyl ammonium bromide functionalized carbon black (CB) anchored platinum nanoparticles as highly efficient oxygen reduction catalysts based on gamma irradiation. The assembled carbon nitride/positive carbon black anchoring PtNPs (Pt/CN2-CB+1) catalyst exhibits significantly improved specific surface area, high graphitization, and uniformly dispersed ultra-small platinum nanoparticles. For the oxygen reduction reaction (ORR) performance, the catalyst shows more positive onset-potential (0.93 V versus RHE) and larger diffusion limiting current density (5.65 mA cm-2) compared with benchmark Pt/C catalysts in alkaline medium. Moreover, the Pt/CN2-CB+1catalyst exhibits a small Tafel slope (92 mV dec-1). Besides, the catalyst was demonstrated the remarkable methanol tolerance and good long-term stability under working conditions. This work provides a new and effectiveγ-rays irradiation for synthesizing the carbon nitride catalysts for energy conversion and storage applications.

"Self-doping" defect engineering in SnP3@gamma-irradiated hard carbon anode for rechargeable sodium storage.

Reasonable design of defect engineering in the electrode materials for sodium-ion batteries (SIBs) can significantly optimize battery performance. Here, compared with the traditional "foreign-doping" defects method, we report an innovative gamma-irradiation technique to introduce the "self-doping" defects in the popcorn hard carbon (HC). Considering the advantages of adsorption-intercalation-alloying sodium storage mechanism, the defect-rich HC-coated alloy structure (SnP3@HC-γ) was integrated. Due to the high energy and strong penetrability of γ-rays, the constructed "self-doping" defect engineering effectively expands the interlayer structure of HC and forms the irregular ring structure. Simultaneously, the exposed large number of coordination unsaturated sites can accelerate the reaction kinetics on the surface. Based on the synergistic effect of the SnP3@HC-γ, the composites exhibit an excellent reversible capacity of 668 mAh g-1 at 0.1 A g-1 in SIBs. Even, after 400 cycles at 1.0 A g-1, an exceptional cyclability with 88% capacity retention (430 mAh g-1) can be maintained. We envision that the γ-irradiation technology used in this research not only overturns the general perception that "self-doping" defects will reduce performance, but also provides reliable technical support for large-scale construction of high-defect, high-capacity and stable sodium-ion anode materials.

Repeated fed-batch strategy and metabolomic analysis to achieve high docosahexaenoic acid productivity in Crypthecodinium cohnii.

BACKGROUND: Docosahexaenoic acid (DHA) is essential for human diet. However, high production cost of DHA using C. cohnii makes it currently less competitive commercially, which is mainly caused by low DHA productivity. In recent years, repeated fed-batch strategies have been evaluated for increasing the production of many fermentation products. The reduction in terms of stability of culture system was one of the major challenges for repeated fed-batch fermentation. However, the possible mechanisms responsible for the decreased stability of the culture system in the repeated fed-batch fermentation are so far less investigated, restricting the efforts to further improve the productivity. In this study, a repeated fed-batch strategy for DHA production using C. cohnii M-1-2 was evaluated to improve DHA productivity and reduce production cost, and then the underlying mechanisms related to the gradually decreased stability of the culture system in repeated fed-batch culture were explored through LC- and GC-MS metabolomic analyses. RESULTS: It was discovered that glucose concentration at 15-27 g/L and 80% medium replacement ratio were suitable for the growth of C. cohnii M-1-2 during the repeated fed-batch culture. A four-cycle repeated fed-batch culture was successfully developed and assessed at the optimum cultivation parameters, resulting in increasing the total DHA productivity by 26.28% compared with the highest DHA productivity of 57.08 mg/L/h reported using C. cohnii, including the time required for preparing seed culture and fermentor. In addition, LC- and GC-MS metabolomics analyses showed that the gradually decreased nitrogen utilization capacity, and down-regulated glycolysis and TCA cycle were correlated with the decreased stability of the culture system during the long-time repeated fed-batch culture. At last, some biomarkers, such as Pyr, Cit, OXA, FUM, L-tryptophan, L-threonine, L-leucine, serotonin, and 4-guanidinobutyric acid, correlated with the stability of culture system of C. cohnii M-1-2 were identified. CONCLUSIONS: The study proved that repeated fed-batch cultivation was an efficient and energy-saving strategy for industrial production of DHA using C. cohnii, which could also be useful for cultivation of other microbes to improve productivity and reduce production cost. In addition, the mechanisms study at metabolite level can also be useful to further optimize production processes for C. cohnii and other microbes.

Shape inducer-free polygonal angle platinum nanoparticles in graphene oxide as oxygen reduction catalyst derived from gamma irradiation.

In this report, polygonal angle platinum nanoparticles (PtNPs) anchored on nitrogen doping reduced graphene oxide (NrGO) as oxygen reduction reaction (ORR) catalyst was synthesized by gamma irradiation assisted with in situ hydrolysis of urea without using any shape inducer, seed, or template. Urea was not only employed as the nitrogen source, but also offered more reductive radicals in the gamma system. The uniform dispersion and homogeneous size distribution of PtNPs are obtained on reduced graphene oxide (rGO), which is attributed to the synergy of restriction effects of GO and crush capacity of high energy gamma rays. In addition, the method simultaneously offers PtNPs with polygonal angle structure and doping nitrogen in rGO, thus provides more surface and corner defects on PtNPs and heteroatomic defects on rGO, which synergistically improve the ORR performance of the samples. The obtained polygonal angle PtNPs modified NrGO exhibit fantabulous ORR activity in alkaline media with enhanced onset potential (906 mV), half-wave potential (783 mV) and superior limit current density (6.74 mA·cm-2) compared to the commercial Pt/C and those PtNPs supported on rGO composites. The results indicate that gamma irradiation assisted with in situ hydrolysis of urea can be a promising candidate method for preparation of high performance Pt-based catalysts in practical application.

Microstructure evolution of sandwich graphite oxide/interlayer-embedded Au nanoparticles induced from γ-rays for carcinoembryonic antigen biosensor.

With the capability of inducing small particle sizes of supported metal in graphite oxide (GO), the γ-ray irradiation method applied for preparing graphite oxide-gold (GO-Au) nanocomposites as electrochemical immunosensors has attracted specific attention recently. To study the accurate factors influencing the precise morphology and final performance of the prepared composites in the γ-irradiation system, we proposed a facile method to investigate the evolution of the GO structure, size and dispersion of Au nanoparticles (AuNPs) produced with the addition of isopropyl alcohol to the system. The GO-Au nanocomposites were characterized by Fourier transform infrared spectroscopy, x-ray diffraction spectra, Raman spectra, x-ray photoelectron spectroscopy and high resolution transmission electron microscopy. These nanocomposites with sandwich morphology exhibited an excellent immunosensor performance with a low detection limit of 15.8 pg ml-1 (S/N = 3) and a wide linear range from 1 to 40 ng ml-1 for detecting carcinoembryonic antigens. The enhanced biosensing performance is attributed to the synergistic effect of γ-irradiation and the precise structure of GO, which endows the smaller size and more uniform distribution of AuNPs on the GO as well as the good signal amplification capability. Furthermore, adopting the γ-irradiation method and use of GO as a precursor is propitious for application in large-scale production because of its high-efficiency and high-yielding characteristics.

Rewiring metabolic network by chemical modulator based laboratory evolution doubles lipid production in Crypthecodinium cohnii.

Dietary omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA, C22:6) can be synthesized in microalgae Crypthecodinium cohnii; however, its productivity is still low. Here, we established a new protocol termed as "chemical modulator based adaptive laboratory evolution" (CM-ALE) to enhance lipid and DHA productivity in C. cohnii. First, ACCase inhibitor sethoxydim based CM-ALE was applied to redirect carbon equivalents from starch to lipid. Second, CM-ALE using growth modulator sesamol as selection pressure was conducted to relive negative effects of sesamol on lipid biosynthesis in C. cohnii, which allows enhancement of biomass productivity by 30% without decreasing lipid content when sesamol was added. After two-step CM-ALE, the lipid and DHA productivity in C. cohnii was respectively doubled to a level of 0.046 g/L/h and 0.025 g/L/h in culture with addition of 1 mM sesamol, demonstrating that this two-step CM-ALE could be a valuable approach to maximize the properties of microalgae.

Nitrogen Feeding Strategies and Metabolomic Analysis To Alleviate High-Nitrogen Inhibition on Docosahexaenoic Acid Production in Crypthecodinium cohnii.

It is well-known that high-nitrogen content inhibits cell growth and docosahexaenoic acid (DHA) biosynthesis in heterotrophic microalgae Crypthecodinium cohnii. In this study, two nitrogen feeding strategies, pulse-feeding and continuous-feeding, were evaluated to alleviate high-nitrogen inhibition effects on C. cohnii. The results showed that continuous-feeding with a medium solution containing 50% ( w/v) yeast extract at 2.1 mL/h during 12-96 h was the optimal nitrogen feeding strategy for the fermentation process, when glucose concentration was maintained at 15-27 g/L during the same period. With the optimized strategy, 71.2 g/L of dry cell weight and DHA productivity of 57.1 mg/L/h were achieved. In addition, metabolomic analysis was applied to determine the metabolic changes during different nitrogen feeding conditions, and the changes in amino acids, polysaccharides, purines, and pentose phosphate pathway were observed, providing valuable metabolite-level information for exploring the mechanism of the high-nitrogen inhibition effect and further improving DHA productivity in C. cohnii.

13C Metabolic Flux Analysis of Enhanced Lipid Accumulation Modulated by Ethanolamine in Crypthecodinium cohnii.

The heterotrophic microalga Crypthecodinium cohnii has attracted considerable attention due to its capability of accumulating lipids with a high fraction of docosahexaenoic acid (DHA). In our previous study, ethanolamine (ETA) was identified as an effective chemical modulator for lipid accumulation in C. cohnii. In this study, to gain a better understanding of the lipid metabolism and mechanism for the positive effects of modulator ETA, metabolic flux analysis was performed using 13C-labeled glucose with and without 1 mM ETA modulator. The analysis of flux distribution showed that with the addition of ETA, flux in glycolysis pathway and citrate pyruvate cycle was strengthened while flux in pentose phosphate pathway was decreased. In addition, flux in TCA cycle was slightly decreased compared with the control without ETA. The enzyme activity of malic enzyme (ME) was significantly increased, suggesting that NADP+-dependent ME might be the major source of NADPH for lipid accumulation. The flux information obtained by this study could be valuable for the further efforts in improving lipid accumulation and DHA production in C. cohnii.

Comparative metabolomic analysis of Crypthecodinium cohnii in response to different dissolved oxygen levels during docosahexaenoic acid fermentation.

Oxygen supply is an important factor during Crypthecodinium cohnii fermentation for docosahexaenoic acid (DHA) production. However, few studies about the intrinsic correlation between dissolved oxygen (DO) and cellular metabolism have been reported. In this study, the responses of C. cohnii to different DO levels were evaluated. The results showed the growth and glucose consumption rates of C. cohnii were much higher under high oxygen supply condition. Furthermore, GC-MS based comparative metabolomic analysis was employed to discriminate the responsive metabolites associated with varying DO levels. The results showed the intermediates involved in glycolytic pathway and TCA cycle were up-regulated under high DO levels at exponential phase. At stationary phase, under high DO levels, metabolites involved in triacylglycerol metabolism were up-regulated, while the OPP pathway intermediate product ribose 5-phosphate was down-regulated. Together, these results provide useful insights into the functional metabolic relationship between DO levels and DHA production in C. cohnii.

Screening of chemical modulators for lipid accumulation in Schizochytrium sp. S31.

Schizochytrium sp. is a promising candidate for docosahexaenoic acid (DHA) production due to its high content of lipid and DHA proportions. To further enhance the lipid accumulation, seven chemical modulators were screened to evaluate their roles on lipid accumulation. Notably, among the seven tested chemical modulators, the addition of naphthoxyacetic acid (BNOA) or jasmonic acid (JA) was able to increase the lipid accumulation of Schizochytrium sp. S31. In addition, the effects of BNOA and JA were demonstrated dose-dependent and time-dependent, achieving a highest increase in lipid content by 11.16% and 12.71% when 2.0 mg/L of BNOA or 20 mg/L of JA was added into culture at 48 h after inoculation, respectively. In addition, the combination of 2 mg/L BNOA and 20 mg/L JA further increased lipid accumulation up to 16.79%. These results provided valuable strategy on promoting the lipid accumulation and DHA production by chemical modulators in Schizochytrium sp. S31.

Small angle X-ray scattering study of microvoid evolution and pertinence of microvoid and mechanical properties in γ-irradiated CFs.

To explore the mechanism of microvoid evolution and the pertinence of microvoid and mechanical behavior of carbon fibers (CFs) in γ-irradiation, T700 CFs were exposed to γ-rays under epoxy chloropropane (ECP) and argon (Ar) at room temperature. The results from small angle X-ray scattering (SAXS) showed that the average microvoid radius of the CFs decreased gradually from 4.8406 nm for pristine fibers to 3.6868 nm (ECP) and 3.4223 nm (Ar), indicating that γ-irradiation could obviously decrease the microvoid in CFs owing to annealing and rearrangement effects. More significantly, active media would enlarge the surface microvoid of fibers, thus the microvoid of CFs irradiated in ECP was overall larger than that in Ar. The tensile strength of CFs was increased from 5.74 GPa for the pristine fibers to 6.78 GPa (Ar) and 6.18 GPa (ECP) for the irradiated CFs along with a decrease in the microvoid. Therefore, this would provide a key to investigate the evolution of the CF microvoid during γ-irradiation, which was conducive to improving the mechanical properties of γ-irradiated CFs.

Screening and transcriptomic analysis of Crypthecodinium cohnii mutants with high growth and lipid content using the acetyl-CoA carboxylase inhibitor sethoxydim.

The heterotrophic microalga Crypthecodinium cohnii is well known for its lipid accumulation, with a high proportion of docosahexaenoic acid (DHA). In this study, we report a novel screening approach to obtain mutants of C. cohnii with high growth and lipid content using the acetyl-CoA carboxylase (ACCase) inhibitor sethoxydim. C. cohnii mutants were generated using atmospheric and room-temperature plasma (ARTP) and then screened for two rounds in media supplemented with sethoxydim. These efforts led to the identification of mutant M-1-2, which had 24.32% higher growth and 7.05% higher lipid content than the wild type, demonstrating the effectiveness of the sethoxydim-based screening. Consistently, the M-1-2 mutant displayed a 16.15% increase in ACCase enzymatic activity and 1.53-fold upregulation of its ACCase-encoding gene based on comparative ACCase activity analysis and transcriptomic analysis, respectively. In addition, transcriptomic analysis showed that transcripts involved in fatty acid biosynthesis, energy, central carbohydrate, and amino acid metabolism were upregulated in the mutant compared to the wild type.

Metabolomic analysis and lipid accumulation in a glucose tolerant Crypthecodinium cohnii strain obtained by adaptive laboratory evolution.

Adaptive laboratory evolution (ALE) was commonly used for strain improvement. Crypthecodinium cohnii is known to accumulate lipids with a high fraction of docosahexaenoic acid (DHA). In order to improve DHA production under high substrate concentration, a glucose-tolerant C. cohnii strain was firstly obtained by ALE after 260 cycles for 650days with gradually increased glucose concentration. The results of lipids content showed that DHA-rich lipids accumulation in the evolved strain could increase by 15.49% at 45g/L glucose concentrations. To reveal mechanisms related to glucose tolerance of C. cohnii through ALE, metabolic profiles were then compared and the results showed that hub metabolites including glycerol, glutamic acid, malonic acid and succinic acid were positively regulated during ALE. The study demonstrated that metabolomic analysis complemented with ALE could be an effective and valuable strategy for basic mechanisms of molecular evolution and adaptive changes in C. cohnii.

The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis.

Although there have been many studies identifying clinical and pathologic factors that may predict central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) patients without clinically cervical lymph node metastasis (cN0), the results were inconsistent. And whether prophylactic central lymph node dissection (pCLND) should be performed in cN0 PTMC remains controversial. The EMBASE, PubMed, MEDLINE and the Cochrane Library were searched until Oct 2015 to identify relevant studies. Primary outcomes were clinical and pathologic factors for CLNM. Secondary outcomes included CLNM rate, surgical complications of hypocalcaemia and recurrent laryngeal nerve(RLN) injury and neck recurrences. Statistical analysis was performed using Stata 12.0. Fourteen eligible studies enrolling 4573 patients were included in this meta-analysis. The overall incidence of CLNM was 33 % (95 % CI 29-37). An elevated risk of CLNM was significantly associated with male gender (OR 2.33, 95 % CI 1.71-3.17), age <45 years (OR 1.27, 95 % CI 1.08-1.48), tumor size >5 mm (OR 2.16, 95 % CI 1.87-2.50), multifocality (OR 1.73, 95 % CI 1.45-2.05), extrathyroidal extension (OR 1.99, 95 % CI 1.66-2.37) and lymphovascular invasion (OR 3.87, 95 % CI 1.64-9.10), but not with thyroid bilaterality (OR 1.41, 95 % CI 0.89-2.22) and chronic lymphocytic thyroiditis (OR 0.98, 95 % CI 0.66-1.47). The pooled frequency of permanent hypocalcaemia, permanent RLN injury and neck recurrences was 1.1, 0.5 and 2.8 %, respectively. cN0 PTMC patients have a considerable CLNM rate and have a low pooled incident of surgical complications and neck recurrences with pCLND. Six unfavorable clinical and pathologic factors, which were significantly associated with CLNM, were identified. These findings may help guide the application of pCLND or subsequent treatment in cN0 PTMC.