Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia.

AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.

Saline-Aided Ultrasound Versus Upper Gastrointestinal Series in Neonates and Infants With Suspected Upper Gastrointestinal Obstruction: A Prospective Multicenter Comparative Study.

BACKGROUND. Use of upper gastrointestinal (UGI) series to diagnose UGI obstruction in neonates and infants has raised concern about increased radiation sensitivity of developing organs. OBJECTIVE. The purpose of this study was to assess the diagnostic performance of saline-aided ultrasound (US) in comparison with UGI series in evaluation for UGI obstruction in neonates and infants. METHODS. In this prospective multicenter study at three hospitals, inpatients were enrolled who were younger than 1 year and had suspected UGI obstruction between June 2015 and May 2018; patients with US evidence of malrotation or pyloric stenosis were ineligible. Enrolled patients underwent both saline-aided US (saline solution administered through a nasogastric tube) and UGI series. Surgical findings or at least 1-year of clinical follow-up findings served as the reference for presence of UGI obstruction. UGI obstruction was classified in terms of level (proximal vs distal) and cause. Two radiologists independently interpreted saline-aided US examinations to assess interobserver agreement and then reached consensus. Two other radiologists assessed upper GI series in consensus. Diagnostic performance for the presence and level of UGI obstruction was compared between modalities. Causes of obstruction were assessed with saline-aided US. RESULTS. A total of 209 neonates were included (116 boys, 93 girls; median age, 5 days; 124 (59.3%) patients had UGI obstruction (proximal in 108 patients). Saline-aided US had strong interobserver agreement for presence (κ = 0.87) and level (κ = 0.85) of obstruction. For presence of UGI obstruction, accuracy, sensitivity, and specificity were 94.7%, 98.4%, and 89.4% for saline-aided US and 89.5%, 95.2%, and 81.2% for UGI series. For obstruction level, accuracy, sensitivity, and specificity were 90.3%, 97.2%, and 56.3% for saline-aided US versus 87.1%, 92.6%, and 50.0% for UGI series. Accuracy for presence was significantly higher for saline-aided US (p = .02); otherwise, these metrics were not different between tests (p > .05). For causes of UGI obstruction (annular pancreas, duodenal web, duodenal atresia, and duodenal stenosis), the accuracy of saline-aided US ranged from 75.0% to 95.2%. CONCLUSION. Saline-aided US has high diagnostic performance for presence and level of UGI obstruction in neonates and infants, comparing favorably with UGI series. Saline-aided US may have additional utility in evaluating causes of obstruction. CLINICAL IMPACT. Saline-aided US may serve as an initial screening modality for UGI obstruction in neonates and infants. TRIAL REGISTRATION. Chinese Clinical Trial Registry ChiCTR-DCC-15006232.

Treatment optimization for recurrent hepatoblastoma: retrospective study from a hepatoblastoma cohort in Southern China.

PURPOSE: The present study aimed to explore the clinical characteristics and optimal treatments of RHB patients. METHODS: We retrospectively collected 42 RHB cases and 161 primary HB (PHB) cases. Clinical characteristics were compared between RHB and PHB patients. The risk factors related to overall survival (OS) and progression-free survival (PFS) in RHB patients were explored by COX regression analysis. Patients were further divided into curable and refractory subgroup by treatments. Propensity score match (PSM) analysis was performed to match recurrent curable patients from 145 curable PHB patients from the same cohort. PFS was further compared between 34 pairs of primary and recurrent curative HB patients. RESULTS: Recurrence treatment and number of relapsed tumors were significantly related with both OS and PFS of RHB patients (p < 0.05). Chemotherapy regimen alteration was also risk factor of PFS for RHB (HR = 4.26; 95% CI = 1.54-11.78; p = 0.005). RHB patients underwent curable treatment had better prognosis, compared with recurrent refractory subgroup (p < 0.001). Matched curable PHB patients demonstrated no significant difference of 3-year PFS with curable RHB patients (p = 0.540). CONCLUSION: Curable RHB patients might get benefit from surgery or ablation with similar prognosis with primary curable HB patients.

Development of a pediatric liver CEUS criterion to classify benign and malignant liver lesions in pediatric patients: a pilot study.

OBJECTIVES: To analyze the contrast-enhanced ultrasound (CEUS) characteristics of pediatric patients with focal liver lesions (FLLs) and develop a pediatric liver CEUS criterion to improve the diagnostic performance of CEUS in differentiating pediatric benign and malignant liver lesions. METHODS: Between March 2011 and May 2020, patients < 18 years who underwent CEUS were retrospectively evaluated. The CEUS characteristics of FLLs were analyzed. A pediatric liver CEUS criterion categorized as CEUS-1 to CEUS-5 was developed. The diagnostic performance of the criterion (i.e., sensitivity, specificity, PPV, and NPV) was assessed. Chi-square and Mann-Whitney tests were used. RESULTS: After exclusion, the study included 130 lesions (mean diameter, 7.1 cm; range, 0.8-17.0 cm) from 130 patients (mean age, 36.0 months; range, 0.03-204.0 months; 74 boys). Hyperenhancement with washout in patients < 5 years or with early washout (≤ 45 s) was used to predict hepatoblastoma, with a sensitivity and specificity of 90.7% (95% confidence interval [CI]: 77.9%, 97.4%) and 93.6% (95% CI: 84.3%, 98.2%), respectively. Peripheral discontinuous globular hyperenhancement was used to diagnose hemangioma, with a sensitivity and specificity of 84.6% (95% CI: 65.1%, 95.6%) and 100% (95% CI: 95.4%, 100.0%), respectively. The rates of malignancies within the pediatric liver CEUS-1, CEUS-2, CEUS-3, CEUS-4, and CEUS-5 categories were 0.0%, 0.0%, 5.6%, 50.0%, and 96.1%, respectively. Besides, the incidences of hepatoblastoma in pediatric liver CEUS-3, CEUS-4, and CEUS-5 were 5.6%, 16.7%, and 67.5%, respectively. CONCLUSIONS: The pediatric liver CEUS criterion is useful in differentiating benign focal liver lesions from malignancies, especially hepatoblastoma from hemangioma. KEY POINTS: • Hyperenhancement with washout in patients

Limited Genetic Connectivity Among Sargassum horneri (Phaeophyceae) Populations in the Chinese Marginal Seas Despite Their high Dispersal Capacity.

Sargassum horneri is a habitat-forming species in the Northwest Pacific and an important contributor to seaweed rafts. In this study, 131 benthic samples and 156 floating samples were collected in the Yellow Sea and East China Sea (ECS) to test the effects of seaweed rafts on population structure and connectivity. Our results revealed high levels of genetic diversity in both benthic and floating samples based on concatenated mitochondrial markers (rpl5-rps3, rnl-atp9, and cob-cox2). Phylogenetic analyses consistently supported the existence of two lineages (lineages I and II), with divergence dating to c. 0.692 Mya (95% HPD: 0.255-1.841 Mya), indicating that long-term isolation may have occurred during the mid-Pleistocene (0.126-0.781 Mya). Extended Bayesian skyline plots demonstrated a constant population size over time in lineage I and slight demographic expansion in lineage II. Both lineages were found in each marginal sea (including both benthic and floating samples), but PCoA, FST , and AMOVA analyses consistently revealed deep genetic variation between regions. Highly structured phylogeographic pattern supports limited genetic connectivity between regions. IMA analyses demonstrated that asymmetric gene flow between benthic populations in the North Yellow Sea (NYS) and ECS was extremely low (ECS→NYS, 2Nm = 0.6), implying that high dispersal capacity cannot be assumed to lead to widespread population connectivity, even without dispersal barriers. In addition, there were only a few shared haplotypes between benthic and floating samples, suggesting the existence of hidden donors for the floating masses in the Chinese marginal seas.

Th17-associated cytokines multiplex testing indicates the potential of macrophage inflammatory protein-3 alpha in the diagnosis of biliary atresia.

BACKGROUND & AIMS: Biliary atresia (BA) is a neonatal obliterative cholangiopathy with high prevalence in south China. Accurate identification of BA among infants with obstructive jaundice is still difficult by noninvasive diagnostic tools. Th17 cells have been reported closely related with the development of BA, which suggest that Th17-associated cytokines were potential biomarkers for the diagnosis of BA patients. METHODS: In the training study, 76 infants who were divided into 2 groups, including BA group (n = 31) and non-BA jaundice group (n = 45). Clinical and routine laboratory data were collected from all subjects. Totally 25 Th17-associated cytokines were tested and compared between groups. The diagnostic value of each differential cytokine was evaluated by the area under the receiver operating characteristic curve (AUC). The best potential diagnostic biomarker was further validated in a cohort including 68 jaundice infants from our partnering institution in a blinded fashion. RESULTS: Data from the training study showed that gamma-glutamyl transferase (GGT) and clay stool would be helpful in the identification of BA patients in jaundice subjects. Th17-associated cytokines assay indicated that IL-17F, IL-10, macrophage inflammatory protein-3alpha (MIP3a), IL-22, IL-13, IL-33, IL-6, IL-17E, IL-27, IL-31, TNF-a and TNF-b were differentially expressed in BA patients, and the AUC of MIP3a was higher than other markers. MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA. The diagnostic value of MIP3a was further confirmed in our validation study. CONCLUSION: MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA.

The Prognostic Value of CD8+ and CD45RO+ T Cells Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation.

BACKGROUND: Postoperative cholangitis is a common but severe complication after Kasai portoenterostomy for biliary atresia (BA). This study aimed to identify its prognostic factors. METHODS: Two sets of liver paraffin-embedded tissue samples were collected from BA patients who received Kasai portoenterostomy (n = 25 and n = 31, respectively). Patients were divided into non-cholangitis and cholangitis groups. The infiltration of CD4+, CD8+, CD45RO+, CD68+ cells and expression of Beclin1 were quantitatively evaluated in immunohistochemical analysis. RESULTS: Cholangitis group had a significantly lower CD8+ T cell infiltration but a higher CD45RO+ cell infiltration, and a lower Beclin1 level than non-cholangitis group (all P < 0.01). Multivariate logistic regression analysis indicated that infiltration of CD8+ cells (odds ratio [OR], 0.112; 95% confidence interval [CI], 0.022-0.577) and CD45RO+ cells (OR, 3.88; 95% CI, 1.37-11.03), and Beclin1 level (OR, 0.088; 95% CI, 0.018-0.452) were independent influence factors for early postoperative cholangitis. Receiver operating characteristic (ROC) analysis showed that area under ROC curve (AUROC) values for CD8+ cells, CD45RO+ cells and Beclin1 were 0.857, 0.738 and 0.900, respectively. CONCLUSION: Our findings demonstrated the CD8+ cells, CD45RO+ cells and Beclin1 level possessed the prognostic value for early postoperative cholangitis following Kasai operation, which may be helpful to develop new prevention and treatment strategies for postoperative cholangitis.

Intestinal obstruction due to dual gastrointestinal atresia in infants: diagnosis and management of 3 cases.

BACKGROUND: Several types of congenital lesions can cause complete or incomplete obstruction of the intestine. Our purpose is to present 3 neonates with dual intestinal type I atresia, i.e., simultaneous obstructive lesions at 2 locations in which the atresia manifested as diaphragm-like tissue. CASE PRESENTATION: All 3 cases were female infants ranging in age from 2 to 14 months. The common symptom in all cases was intermittent persistent vomiting. In some cases the vomitus was bilious, and other symptoms included abdominal distention and delayed meconium passage. Prior surgeries at another hospital were unsuccessful at relieving the symptoms in one case. One case had dual lesions in the colon, one dual lesions in the duodenum, and one atresia at both the distal portion of the ileum and the descending colon. Surgical exploration and removal of the lesions at our hospital was successful in all cases, and the infants were discharged in good condition. CONCLUSIONS: Type I atresia can manifest as a diaphragm-like tissue obstructing the continuity of gastrointestinal tract, and in rare cases multiple areas may be present. Base on the intermittent nature of the associated symptoms, diagnosis can be difficult and is often delayed. Physicians should be aware of this condition during the work-up of an infant with persistent intermittent vomiting.

The ever-lasting green tides: What can we do？.

Macroalgal blooms (Green tides) are occurring more frequently in many regions of the world because of the combined effects of increasingly intense human activity and climate change. In the last decade, the world's largest Ulva prolifera green tide has become a recurrent phenomenon, appearing every summer in the southern Yellow Sea, China. Green tides can hurt coastal tourism and eradicate aquaculture and artisanal fishing. Eutrophication in nearshore waters is the ultimate explanation for the explosive growth of the macroalgal biomass, but the specific course of each nearshore green tide is often complex and requires in-depth and extensive research to develop effective mitigation strategies. Researchers have undertaken extensive studies on the prevention, control and mitigation of large-scale green algal blooms, and felicitated the utilization of green tide harmful biomass through bio-refining, bioconversion and other measures. However, due to the large-scale and trans-regional nature of the green tide, the government's administrative coordination measures are also essential for effective control. Nevertheless, it is becoming increasingly urgent to prevent and control the bloom at the early stage, and efficiently salvage and use these valuable raw materials.

Phycosphere bacterial disturbance of Saccharina japonica caused by white rot disease relates to seawater nutrients.

In mid-November 2021, there were large areas of white rot disease on cultivated Saccharina japonica in Rongcheng City, China, and diseases were undetected on Sargassum horneri and Porphyra yezoensis. The disturbance direction of bacterial community in the phycosphere after disease outbreak and the relationship with seawater nutrients remain unclear. Here, in situ studies of bacterial community in the non-diseased and diseased areas (Shawo and Dongchu islands) and seawater nutrient levels were carried out. 16S rRNA sequencing showed that the bacterial richness of the studied seaweeds increased in the diseased area. Only in S. japonica, Algitalea outcompeted abundant primary bacteria with probiotic relationships to the host of the non-diseased area, and dominated in the diseased area (17.6% of the total abundance). Nitrogen and phosphorus levels in seawater were 57.8% and 19.6% higher in the non-diseased area than those in the diseased area, respectively, and were strongly correlated with the phycosphere bacteria at the family level of S. japonica. There was no difference in potential pathogenicity between the two areas, while positive signal communications decreased, and nitrogen cycle, chemoheterotrophy, and cellulolysis increased in the diseased area compared to the non-diseased area. Overall, white rot disease caused a structural disturbance in phycosphere bacterial community of S. japonica that related to seawater nutrient levels. Enriched degraders and altered bacterial community functions may exacerbate the disease. This evaluation will provide information for white rot disease management to prevent and mitigate the occurrence of S. japonica outbreaks.

Mucosal-associated invariant T cells promote ductular reaction through amphiregulin in biliary atresia.

BACKGROUND: Biliary atresia (BA) is a neonatal fibro-inflammatory cholangiopathy with ductular reaction as a key pathogenic feature predicting poor survival. Mucosal-associated invariant T (MAIT) cells are enriched in human liver and display multiple roles in liver diseases. We aimed to investigate the function of MAIT cells in BA. METHODS: First, we analyzed correlations between liver MAIT cell and clinical parameters (survival, alanine transaminase, bilirubin, histological inflammation and fibrosis) in two public cohorts of patients with BA (US and China). Kaplan-Meier survival analysis and spearman correlation analysis were employed for survival data and other clinical parameters, respectively. Next, we obtained liver samples or peripheral blood from BA and control patients for bulk RNA sequencing, flow cytometry analysis, immunostaning and functional experiments of MAIT cells. Finally, we established two in vitro co-culture systems, one is the rhesus rotavirus (RRV) infected co-culture system to model immune dysfunction of human BA which was validated by single cell RNA sequencing and the other is a multicellular system composed of biliary organoids, LX-2 and MAIT cells to evaluate the role of MAIT cells on ductular reaction. FINDINGS: Liver MAIT cells in BA were positively associated with low survival and ductular reaction. Moreover, liver MAIT cells were activated, exhibited a wound healing signature and highly expressed growth factor Amphiregulin (AREG) in a T cell receptor (TCR)-dependent manner. Antagonism of AREG abrogated the proliferative effect of BA MAIT cells on both cholangiocytes and biliary organoids. A RRV infected co-culture system, recapitulated immune dysfunction of human BA, disclosed that RRV-primed MAIT cells promoted cholangiocyte proliferation via AREG, and further induced inflammation and fibrosis in the multicellular system. INTERPRETATION: MAIT cells exhibit a wound healing signature depending on TCR signaling and promote ductular reaction via AREG, which is associated with advanced fibrosis and predictive of low survival in BA. FUNDING: This work was funded by National Natural Science Foundation of China grant (82001589 and 92168108), National Key R&D Program of China (2023YFA1801600) and by Basic and Applied Basic Research Foundation of Guangdong (2020A1515110921).

Ex vivo tumor dissection followed by kidney autotransplantation in bilateral wilms tumor.

Introduction: Successful management of bilateral Wilm's tumor (BWT) involves a radical resection while preserving enough normal kidney tissue. Nephron-sparing surgery often results in an R1/R2 resection with a high recurrence rate in children with huge or multiple tumors, or tumors proximity to the renal hilum. In contrast, kidney autotransplantation can completely resect the tumor while maintaining homeostasis and preserving the patient's healthy kidney tissues. Methods: We summarized the clinical data of 8 synchronous BWT patients who underwent kidney autotransplantation at the First Affiliated Hospital of Sun Yat-sen University from 2018 to 2020. Ex vivo tumor resection and kidney autotransplantions were performed on 11 kidneys. The baseline characteristics, perioperative management, and survival status were reported. Results: Nephron-sparing surgeries were performed on 5 kidneys in vivo. Among all the 8 patients, six of them (75%) received staged operation and the other 2 patients (25%) received single-stage operation. No residual tumors were found on the postoperative imaging in all the 8 patients. In total, 6 (75%) patients occurred complications after the autotransplantation, among which, 2 (33.3%) patients had complication of Clavien-Dindo grade IIIa, and 4 (66.7%) patients had complication of grade < 3. During the 38 months of follow-up, 87.5% (7/8) of patients were tumor-free survival with normal renal function. One patient died from renal failure without tumor recurrence. Discussion: Therefore, our study indicated that autologous kidney transplantation can be an option for patients with complex BWT if the hospital's surgical technique and perioperative management conditions are feasible.

Surgical Strategy and Application of Robotic-Assisted Benign Sacral Neurogenic Tumor Resection.

BACKGROUND: Robotic surgery may be advantageous in neurogenic sacral tumor resection but only a few studies reported robotic-assisted neurogenic sacral tumor resection. OBJECTIVE: To propose a new surgical strategy for robotic-assisted benign sacral neurogenic tumor resection and introduce the ultrasonic osteotomy surgical system in robotic surgery. METHODS: Twelve patients who had robotic-assisted primary benign sacral neurogenic tumor resection between May 2015 and March 2021 were included. Our surgical strategy divides tumors into 4 types. Type I: Presacral tumors with diameter <10 cm. Type II: Narrow-base tumors involving the sacrum with diameter <10 cm. Type III: Broad-base tumors involving the sacrum with diameter <10 cm. Type IV: Tumors involving sacral nerve roots ≥2 levels and/or with diameter ≥10 cm. RESULTS: Five type I, 5 type II, and 1 type III patients underwent tumor resection via an anterior approach, and 1 type IV patient via a combined approach. The median operation time, blood loss, and postoperative hospital stay of type I and II were much less than those of type IV. The ultrasonic osteotomy surgical system facilitated osteotomy in 2 type II and 1 type III patients. Eleven patients had total resections, and 1 type III patient had a partial resection. During the follow-up period of 7.9 to 70.9 months (median: 28.5 months), no local recurrences or deaths were noted. CONCLUSION: With the largest single-center series to our knowledge, this surgical strategy helped to guide robotic-assisted benign sacral neurogenic tumor resection. The ultrasonic osteotomy surgical system was effective for type II and III.

Effects of instantaneous changes in temperature, light, and salinity on the dynamics of dissolved organic carbon release by Sargassum thunbergii.

Although macroalgae are regarded as the emerging fourth category of "blue carbon", few studies are available on the dynamics of dissolved organic carbon (DOC) release. Sargassum thunbergii is a typical intertidal macroalgae; and tidal action usually triggers instantaneous changes in temperature, light and salinity. Therefore, we investigated the mechanism of short-term changes in temperature, light and salinity on DOC release by S. thunbergii. As well as these factors coupled with desiccation, the combined effect of DOC release was revealed. The results showed the DOC release rate of S. thunbergii was from 0.028 to 0.037 mg C g -1(FW) h-1 under different photosynthetically active radiation (PAR, 0-1500 µmol photons m-2 s-1). The DOC release rate of S. thunbergii was from 0.008 to 0.208 mg C g -1(FW) h-1 under different salinity (5-40). The DOC release rate of S. thunbergii was from 0.031 to 0.034 mg C g -1(FW) h-1 under different temperature (10-30 °C). Either the increase in intracellular organic matter concentration due to increased photosynthesis (change in PAR and temperature, active), cell dehydration due to dry-out process (passive) or the decrease in extracellular salt concentration (passive) would lead to an increase in the difference in osmotic pressure and promote DOC release.

Ocean acidification exacerbates the inhibition of fluctuating light on the productivity of Ulva prolifera.

Ulva prolifera, a common species of green macroalgae, is often harmful-algal-bloom causative and significantly impacts local marine ecosystems. Previous studies on the physiological characteristics of U. prolifera have been conducted under constant light (CL). However, light in the natural environment continually changes, and little is known about fluctuating light (FL). Ocean acidification (OA) has been proposed to interact with dynamic surrounding environments to affect the physiological performance of macroalgae. Therefore, we investigated the combined effects of FL (80/300, alternating between 80 µmol photons m-2 s-1 for 2.5 h and 300 µmol photons m-2 s-1 for 1.5 h, with an average light intensity of 160 µmol photons m-2 s-1 and OA (1000 ppm CO2) on U. prolifera. The results clearly showed that FL had no significant effect on the relative growth rate (RGR), whereas OA obviously improved RGR. However, under FL-OA combination conditions, RGR was inhibited significantly, accompanied by a concomitant downgraded photosynthetic performance, while the photoprotective abilities were enhanced. The results would help us accurately predict the primary productivity of macroalgae in coastal waters under future OA conditions with irradiance fluctuations.

METTL3-mediated N6-methyladenosine modification of DUSP5 mRNA promotes gallbladder-cancer progression.

N6-methyladenosine (m6A) RNA methylation and its associated methyltransferase METTL3 play an important role in tumorigenesis of a series of tumors. However, dysregulation of METTL3 in gallbladder cancer (GBC) remains obscure. Here, we showed that upregulated METTL3 level predicted poor prognosis and correlated with increased lymphatic metastasis and high TNM stage. Functionally, we found that METTL3 could promote cell proliferation, invasion, and migration of GBC-SD and NOZ cells. Mechanistically, we revealed the METTL3-mediated m6A-modification profile in GBC cells and identified DUSP5 as the downstream gene of METTL3. METTL3 promoted the degradation of DUSP5 mRNA in a YTHDF2-dependent manner. Rescue assays showed that downregulation of DUSP5 could attenuate the knockdown METTL3-mediated inhibition of cell proliferation, invasion, and migration of GBC-SD and NOZ cells. Thus, our finding shows that elevated METTL3 expression contributes to tumor aggression in GBC, suggesting that METTL3 is a possible prognostic predictor and therapeutic target against GBC.

Physiological acclimation of Ulva prolifera to seasonal environmental factors drives green tides in the Yellow Sea.

To understand how seasonal factors could drive the formation of green tide blooms and their flotation and decay, we cultured the green tide algal species Ulva prolifera at various temperatures (5, 10, 15, 20, 25, 30, and 35 °C) and light intensities (40, 80, 140, 240, and 400 µmol photons m-2 s-1). The results showed that the ratio of floating U. prolifera increased with increasing light and temperature, which was accompanied by morphological changes. The net photosynthetic rate and the proportion of floating U. prolifera thalli showed a nonlinear relationship. Furthermore, an enclosure experiment confirmed that the flotation of U. prolifera was influenced by light intensity via the regulation of photosynthesis of the thalli. These results suggest that seasonal factors control the photosynthesis of U. prolifera, which drives the flotation and decay of green tide algae in the Yellow Sea.

Integrated biotechnology to mitigate green tides.

Around the world, green tides are happening with increasing frequency because of the dual effects of increasingly intense human activity and climate change; this leads to significant impacts on marine ecology and economies. In the last decade, the world's largest green tide, which is formed by Ulva/Enteromorpha porifera, has become a recurrent phenomenon every year in the southern Yellow Sea (China), and it has been getting worse. To alleviate the impacts of such green tide outbreaks, multiple measures need to be developed. Among these approaches, biotechnology plays important roles in revealing the outbreak mechanism (e.g., molecular identification technology for algal genotypes), controlling and preventing outbreaks at the origin sites (e.g., technology to inhibit propagation), and utilizing valuable algal biomass. This review focuses on the various previously used biotechnological approaches that may be applicable to worldwide seaweed blooms that result from global climate change and environmental degradation.

A joint transcriptional regulatory network and protein activity inference analysis identifies clinically associated master regulators for biliary atresia.

Biliary atresia (BA) is a devastating cholangiopathy in neonate. Transcription factors (TFs), a type of master regulators in biological processes and diseases, have been implicated in pathogenesis of BA. However, a global view of TFs and how they link to clinical presentations remain explored. Here, we perform a joint transcriptional regulatory network and protein activity inference analysis in order to investigate transcription factor activity in BA. By integration of three independent human BA liver transcriptome datasets, we identify 22 common master regulators, with 14 activated- and 8 repressed TFs. Gene targets of activated TFs are enriched in biological processes of SMAD, NF-kappaB and TGF-beta, while those of repressed TFs are related to lipid metabolism. Mining the clinical association of TFs, we identify inflammation-, fibrosis- and survival associated TFs. In particular, ZNF14 is predictive of poor survival and advanced live fibrosis. Supporting this observation, ZNF14 is positively correlated with T helper cells, cholangiocytes and hepatic stellate cells. In sum, our analysis reveals key clinically associated master regulators for BA.

A Perspective on Developing a Plant 'Holobiont' for Future Saline Agriculture.

Soil salinity adversely affects plant growth and has become a major limiting factor for agricultural development worldwide. There is a continuing demand for sustainable technology innovation in saline agriculture. Among various bio-techniques being used to reduce the salinity hazard, symbiotic microorganisms such as rhizobia and arbuscular mycorrhizal (AM) fungi have proved to be efficient. These symbiotic associations each deploy an array of well-tuned mechanisms to provide salinity tolerance for the plant. In this review, we first comprehensively cover major research advances in symbiont-induced salinity tolerance in plants. Second, we describe the common signaling process used by legumes to control symbiosis establishment with rhizobia and AM fungi. Multi-omics technologies have enabled us to identify and characterize more genes involved in symbiosis, and eventually, map out the key signaling pathways. These developments have laid the foundation for technological innovations that use symbiotic microorganisms to improve crop salt tolerance on a larger scale. Thus, with the aim of better utilizing symbiotic microorganisms in saline agriculture, we propose the possibility of developing non-legume 'holobionts' by taking advantage of newly developed genome editing technology. This will open a new avenue for capitalizing on symbiotic microorganisms to enhance plant saline tolerance for increased sustainability and yields in saline agriculture.