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Ji-Rong Yang,1 Ying-Yuan Li,2 Tao-Jia Ran,1 Xiao-Yu Lin,1 Jin-Yan Xu,1 Shao-Li Zhou,1 Pin-Jie Huang1 1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, Huadu District People’s Hospital, Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Pin-Jie Huang; Shao-Li Zhou, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of China, Email hpjie@126.com; 13610272308@139.comPurpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA).Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine (group ED, n=76), 0.5-μg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications.Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P < 0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P < 0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P < 0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P< 0.0001).Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.Plain language summary: Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.Keywords: cesarean section, dexmedetomidine, esketamine, CSEA, visceral pain

Gui-Qi Zhu,1,2,* Kang Wang,3,* Biao Wang,1,2,* Yu-Jie Zhou,4,* Yi Yang,1,2 Er-Bao Chen,5 Zheng-Jun Zhou,1,2 Shao-Lai Zhou,1,2 Ying-Hong Shi,1,2 Jian Zhou,1,2 Zhi Dai1,2 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 2State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China; 3Department of Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 400016, China; 4Department of Gastroenterology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China; 5Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Background and aim: To investigate the value of the aspartate aminotransferase-to-platelet ratio index (APRI) and build a new nomogram for hepatocellular carcinoma (HCC) patients undergoing postoperative adjuvant transarterial chemoembolization (PATACE).Methods: We retrospectively reviewed 351 patients with HCC undergoing PATACE. We collected baseline HCC patient characteristics to obtain the risk factors for determining poor disease-free survival (DFS) and early time to recurrence (TTR) after PATACE. The multivariate Cox proportional hazards model was used to build new nomogram based on significant prognostic factors of outcomes.Results: We generated the cutoff value of the APRI as 0.50 using the X-tile to distinguish patients with different outcomes in the whole cohort. Two hundred seventeen patients with high APRI had poorer survival (P

Changsheng Yan,1 Yi Jiang,1 Yicong Wan,1 Lin Zhang,2 Jinhui Liu,1 Shulin Zhou,1 Wenjun Cheng1 1Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, 2Department of Obstetrics and Gynecology, Zhongda Hospital Affiliated to Southeast University, Medical School, Southeast University, Nanjing, Jiangsu, People’s Republic of China Abstract: Long noncoding RNA (lncRNA) has been proven to be involved in many biological processes in ovarian cancer (OC). However, the mechanism still remains unknown. In this study, we screened significantly downregulated NBAT-1, which has been proven to play a significant role in breast cancer, clear cell renal cell carcinoma, and neuroblastoma, but not in OC, in two independent datasets with relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to normal ovarian tissue (P

Abstract We study antiperiodic boundary value problems for semilinear differential and impulsive differential equations in finite dimensional spaces. Several new existence results are obtained.

Phosphorus deficiency usually promotes root:shoot ratio and sugar accumulation. However, how the allocation and utilization of carbon assimilates are regulated by phosphorus deficiency remains unclear. To understand how phosphorus deficiency affects the allocation and utilization of carbon assimilates, we systematically investigated the fixation and utilization of carbon, along with its diurnal and spatial patterns, in hydroponically grown maize seedlings under low phosphorus treatment. Under low phosphorus, sucrolytic activity was slightly inhibited by 12.0% in the root but dramatically inhibited by 38.8% in the shoot, corresponding to the promoted hexose/sucrose ratio and biomass in the root. Results point to a stable utilization of sucrose in the root facilitating competition for more assimilates, while increasing root:shoot ratio. Moreover, starch and sucrose accumulated in the leaves under low phosphorus. Spatially, starch and sucrose were oppositely distributed, starch mainly in the leaf tip, and sucrose mainly in the leaf base and sheath. Evidence of sucrose getting stuck in leaf base and sheath suggests that carbon accumulation is not attributed to carbon assimilation or export disturbance, but may be due to poor carbon utilization in the sinks. These findings improve the understanding of how low phosphorus regulates carbon allocation between shoot and root for acclimation to stress, and highlight the importance of improving carbon utilization in sinks to deal with phosphorus deficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC., Patients and Methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time., Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort., Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective: To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma. Methods: The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53]. Results: A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t =-2.932, P =0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t =-4.45, P <0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%. Conclusions: Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

Synthetic cathinones, which are novel psychoactive substances, have caused major social problems worldwide. A substance called 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP), which is employed as a commercial industrial photoinitiator for triggering polymerization, has a basic cathinone backbone; however, few reports regarding MMMP have been published. In the current study, three potential metabolites of MMMP-namely hydroxy-MMMP (HO-MMMP), HO-MMMP-sulfoxide (HO-MMMP-SO), and HO-MMMP-sulfone (HO-MMMP-SO 2 )-were successfully synthesized, and MMMP and these three potential metabolites were used as standards to establish an analytic method based on liquid chromatography-tandem mass spectrometry for the quantitative analysis of urine. This analytic method and related parameters-including dynamic range, limit of quantification, selectivity, precision, accuracy, carryover effect, matrix effect, interference, and dilution integrity-were optimized and validated. Forty urine samples from 1,691 individuals who abused drugs were determined to contain MMMP, HO-MMMP, HO-MMMP-SO, or HO-MMMP-SO 2 ; the results of this study indicate that approximately 2.37 % of drug abusers in Taiwan consumed MMMP in 2023. These 40 urine samples were analyzed to investigate the metabolism of MMMP in humans. The results indicate that HO-MMMP-SO is the main metabolite in human urine. This study recommends HO-MMMP-SO with a concentration of 2 ng/mL as a target and cutoff value, respectively, for identifying individuals who have consumed MMMP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In order to explore the evolution law and driving mechanism of aerobic denitrification bacteria in Baiyangdian Lake under different hydrological scenarios, based on water quality survey and high-throughput sequencing technology, this study conducted a water quality factor analysis and aerobic denitrification bacteria α -diversity analysis, species composition, and network analysis. The results showed that the water body of Baiyangdian Lake was weakly alkaline, with the highest T and the lowest DO in the rainy season and the lowest T and the highest DO in the freezing season. There were significant differences between NH 4 + -N, NO 2 - -N, NO 3 - -N, TN, permanganate index, Fe, and Mn in Baiyangdian water under different hydrological scenarios ( P &lt; 0.01), and there was no significant difference in TP under different hydrological scenarios ( P &gt; 0.05). The largest category in water bodies under different hydrological scenarios was Proteobacteria, and the genera with a higher relative abundance were Magnetospirillum , Aeromonas , Pseudomonas , Azospirillum , and Bradyrhizobium . In addition, within the aerobic denitrifying bacteria community, there were significant differences in α -diversity ( P &lt; 0.001), with the highest abundance of microbial communities occurring during the freezing period, and the highest diversity and evenness of microbial communities during the dry and freezing periods. According to the RDA and Mantel analyses, the water quality driving factors of flora were different under different hydrological scenarios. The water quality driving factors of flora in the dry season were pH, NO 3 - -N, NO 2 - -N, and permanganate index; the driving factors of flora in the rainy season were pH, T , DO, NO 2 - -N, and TP; the driving factors of flora in the normal season were NO 2 - -N, Fe, and permanganate index; and the driving factors of flora in the freezing season were NO 3 - -N and NONO 2 - -N. Network analysis showed that there were temporal differences in species related to water quality driving factors. The genera related to water quality driving factors during the dry season were Magnetospirillum , Aeromonas , and Azoarcus , whereas the genera related to the rainy season were Magnetospirillum , Pseudomonas , and Aeromonas . The genera related to the normal season were Magnetospirillum , Pseudomonas , and Limnohabitans , and the genera related to the freezing period were Magnetospirillum , Azoarcus , and Pseudomonas . The relationship between key water quality factors (mainly T , DO, NO 3 - -N, and permanganate index) and aerobic denitrification flora in different hydrological scenarios was gradually changing with time. In conclusion, the study on the evolution characteristics of aerobic denitrification bacteria in Baiyangdian Lake under different hydrological scenarios and the driving mechanism of environmental factors could provide a basis for understanding the evolution mechanism of aerobic denitrification bacteria in the natural environment.

Objective: The aim of this study is to examine the perception, willingness to engage, and demand of community residents regarding the 'internet + nursing service' in a designated pilot area, aiming to offer insights for the widespread adoption of the 'internet + nursing service' throughout China., Methods: A survey pertaining to the 'internet + nursing service' was conducted from March to April 2022. The study specifically targeted residents within two sub-districts of a city in the Jiangsu province. The sampling technique employed in this study was stratified random sampling., Results: Out of a total of 400 community residents selected from two sub-districts in this region, 378 provided valid responses, resulting in an effective rate of 94.5%. Within the study cohort, 80 participants (21.16%) demonstrated familiarity with the concept of 'internet + nursing service.' Additionally, 231 participants (61.11%) conveyed their willingness to adopt such services. Regarding service preferences, the primary demands were for health guidance, vital sign monitoring, and basic care. Challenges in implementing the service were attributed to concerns related to medical risks, personal safety for both nurses and patients, and potential breaches of privacy., Conclusions: Residents in the pilot area exhibited a moderate awareness of the 'internet + nursing service,' with a relatively high willingness to embrace the program. There is a need for further refinement of pertinent laws, widespread dissemination of policies, and enhancements in the quality of nursing services. These measures aim to ensure that a greater number of community residents can avail themselves of improved home-based nursing services.

Background: Accurately assessing the prognosis of patient with large-scale cerebral infarction caused by acute middle cerebral artery (MCA) occlusion in the early stages of onset can help clinicians to actively and effectively intervene, thus reducing mortality and disability rates. This study set out to investigate the predictive value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) on collateral circulation and clinical prognosis., Methods: The clinical data of 70 patients admitted to The First People's Hospital of Lianyungang from January 2018 to December 2021 with acute cerebral infarction due to occlusion of the proximal end of the M1 segment in the MCA were retrospectively collected. All patients had their first onset of disease and did not receive thrombolytic therapy at the time of onset. Subsequently, they underwent endovascular thrombectomy for treatment. The FVH and collateral vessel scores were derived according to patients' fluid-attenuated in version recovery (FLAIR) sequence and time-of-flight magnetic resonance angiography images. Based on the 90-day Modified Rankin Scale (mRS), patients were allocated to a good prognosis group (mRS ≤2) and a poor prognosis group (mRS =3-6). The correlation between the FVH and collateral vessel scores was assessed using the Spearman rank correlation test. Pearson correlation coefficient analysis was used to assess the correlation between FVH and the 90-day mRS together with the infarct size. Univariate analysis, multivariate binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were adopted to identify those factors potentially. associated with the prognosis of patients with acute ischemic stroke (AIS)., Results: Out of 70 patients with acute unilateral MCA occlusion (MCAO) who met the inclusion criteria, 62 showed positive FVH sign. These 62 patients were divided into a good prognosis group (n=32) and a poor prognosis group (n=30) based on the mRS score 90 days after discharge. The Spearman rank correlation test indicated that FVH was positively correlated with collateral vessel grade (Spearman rho =0.865; P<0.001); meanwhile, Pearson correlation coefficient analysis indicated that FVH score had moderate negative correlation with 90-day mRS score (r=-0.605; P<0.001). The results of multivariate binary logistic regression analysis indicated that collateral vessel grade and FVH score may be associated with the prognosis of patients with AIS, and the area under the curve (AUC) of FVH score was larger than collateral vessel grade (AUC =0.738)., Conclusions: There was a positive correlation between FVH score and collateral vessel grade, and FVH score could indicate collateral circulation. FVH score was negatively correlated with 90-day mRS score and infarct volume and thus can predict clinical prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1640/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a 245 and a 355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E 2 /E 3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River &gt; Baigouyin River &gt; Fuhe River &gt; Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components ( P &gt;0.05), but there were differences among the C2 and C3 components ( P &lt;0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.

The JASMONATE ZIM DOMAIN (JAZ) proteins are a key inhibitors of the jasmonic acid (JA) signaling pathway that play an important role in the regulation of plant growth and development and environmental stress responses. However, there is no systematic identification and functional analysis of JAZ gene family members in sugarcane. In this study, a total of 49 SsJAZ genes were identified from the wild sugarcane species Saccharum spontaneum genome that were unevenly distributed on 13 chromosomes. Phylogenetic analysis showed that all SsJAZ members can be divided into six groups, and most of the SsJAZ genes contained photoreactive and ABA-responsive elements. RNA-seq analysis revealed that SsJAZ1-1/2/3/4 and SsJAZ7-1 were significantly upregulated under drought stress. The transcript level of ScJAZ1 which is the homologous gene of SsJAZ1 in modern sugarcane cultivars was upregulated by JA, PEG, and abscisic acid (ABA). Moreover, ScJAZ1 can interact with three other JAZ proteins to form heterodimers. The spatial and temporal expression analysis showed that SsJAZ2-1/2/3/4 were highly expressed in different tissues and growth stages and during the day-night rhythm between 10:00 and 18:00. Overexpression of ScJAZ2 in Arabidopsis accelerated flowering through activating the expression of AtSOC1, AtFT, and AtLFY. Moreover, the transcription level of ScJAZ2 was about 30-fold in the early-flowering sugarcane variety than that of the non-flowering variety, indicating ScJAZ2 positively regulated flowering. This first systematic analysis of the JAZ gene family and function analysis of ScJAZ1/2 in sugarcane provide key candidate genes and lay the foundation for sugarcane breeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Vanadium oxides have aroused attention as cathode materials in aqueous zinc-ion batteries (AZIBs) due to their low cost and high safety. However, low ion diffusion and vanadium dissolution often lead to capacity decay and deteriorating stability during cycling. Herein, vanadium dioxides (VO 2 ) nanobelts are coated with a single-atom cobalt dispersed N-doped carbon (Co-N-C) layer via a facile calcination strategy to form Co-N-C layer coated VO 2 nanobelts (VO 2 @Co-N-C NBs) for cathodes in AZIBs. Various in-/ex situ characterizations demonstrate the interfaces between VO 2 layers and Co-N-C layers can protect the VO 2 NBs from collapsing, increase ion diffusion, and enhance the Zn 2+ storage performance. Additional density functional theory (DFT) simulations demonstrate that Co─O─V bonds between VO 2 and Co-N-C layers can enhance interfacial Zn 2+ storage. Moreover, the VO 2 @Co-N-C NBs provided an ultrahigh capacity (418.7 mAh g -1 at 1 A g -1 ), outstanding long-term stability (over 8000 cycles at 20 A g -1 ), and superior rate performance., (© 2023 Wiley‐VCH GmbH.)

Background: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC., Methods: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC., Results: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS., Conclusion: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC., (© 2024. Japanese Society of Gastroenterology.)

Drought-induced leaf senescence is associated with high sugar levels, which bears some resemblance to the syndrome of diabetes in humans; however, the underlying mechanisms of such 'plant diabetes' on carbon imbalance and the corresponding detoxification strategy are not well understood. Here, we investigated the regulatory mechanism of exogenous methylglyoxal (MG) on 'plant diabetes' in maize plants under drought stress applied via foliar spraying during the grain-filling stage. Exogenous MG delayed leaf senescence and promoted photoassimilation, thereby reducing the yield loss induced by drought by 14%. Transcriptome and metabolite analyses revealed that drought increased sugar accumulation in leaves through inhibition of sugar transporters that facilitate phloem loading. This led to disequilibrium of glycolysis and overaccumulation of endogenous MG. Application of exogenous MG up-regulated glycolytic flux and the glyoxalase system that catabolyses endogenous MG and glycation end-products, ultimately alleviating 'plant diabetes'. In addition, the expression of genes facilitating anabolism and catabolism of trehalose-6-phosphate was promoted and suppressed by drought, respectively, and exogenous MG reversed this effect, implying that trehalose-6-phosphate signaling in the mediation of 'plant diabetes'. Furthermore, exogenous MG activated the phenylpropanoid biosynthetic pathway, promoting the production of lignin and phenolic compounds, which are associated with drought tolerance. Overall, our findings indicate that exogenous MG activates defense-related pathways to alleviate the toxicity derived from 'plant diabetes', thereby helping to maintain leaf function and yield production under drought., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets., Materials and Methods: In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 ( BLACAT1 ) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1 . During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining., Results: lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues ( p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1 's promotion of HSCC cell proliferation ( p < 0.05), migration ( p < 0.01), and invasion ( p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1 -binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation ( p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group ( p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group ( p < 0.01)., Conclusions: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo . This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.

Aims: Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT., Methods: 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups., Results: According to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025)., Conclusions: Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

X chromosome inactivation can balance the effects of the two X chromosomes in females, and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation. The mechanisms of escape include modification of DNA, RNA, histone, epitope, and various regulatory proteins, as well as the spatial structure of chromatin. The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases, particularly autoimmune diseases. It has been demonstrated that the presence of TLR7, CD40L, IRAK-1, CXCR3, and CXorf21 significantly contributes to the prevalence of SLE (systemic lupus erythematosus) in females. This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus. Therefore, elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease, but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.

The polysaccharides extracted from Aspidopterys obcordata are thought to have anti-urolithiasis activity in Drosophila kidney stones. This study aimed to assess the effects of different extraction solvents on the yield, chemical composition, and bioactivity of polysaccharides from A. obcordata . A. obcordata polysaccharides were extracted by using four solutions: hot water, HCl solution, NaOH solution, and 0.1 M NaCl. The results revealed that the extraction solvents significantly influenced the extraction yields, molecular weight distribution, monosaccharide compositions, preliminary structural characteristics, and microstructures of polysaccharides. The NaOH solution's extraction yield was significantly higher than the other extraction methods. Vitro antioxidant activity assays revealed that the NaOH solution extracted exhibited superior scavenging abilities towards DPPH and ABTS radicals and higher FRAP values than other polysaccharides. The vitro assays conducted for calcium oxalate crystallization demonstrated that four polysaccharides exhibited inhibitory effects on the nucleation and aggregation of calcium oxalate crystals, impeded calcium oxalate monohydrate growth, and induced calcium oxalate dihydrate formation. The NaOH solution extracted exhibited the most pronounced inhibition of calcium oxalate crystal nucleation, while the hot water extracted demonstrated the most significant suppression of calcium oxalate crystal aggregation. Therefore, it can be inferred that polysaccharides extracted with NaOH solution exhibited significant potential as a viable approach for extracting polysaccharides from stems due to their superior yield and the remarkable bioactivity of the resulting products.

Background: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction., Objective: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale., Methods: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment., Discussion: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The bromodomain is a highly conserved protein domain that specifically binds to acetylated lysine residues in histones, thereby activating transcription of target genes. Although some progress in Global Transcription Factor Group E (GTE) has been achieved in numerous animals and a few plant species, no systematic analysis of GTE gene families has been reported yet in sugarcane. In our study, 37 GTE and GTE-Like (GTEL) genes were characterized in the Saccharum spontaneum. All SsGTE/SsGTEL members were heterogeneously located on all chromosomes of the sugarcane genome and divided into five groups. Transcriptome data showed that SsGTEL3a was expressed at significantly higher levels under drought stress in drought-resistant varieties than in drought-sensitive varieties. Moreover, the overexpression of SsGTEL3a significantly improved the drought tolerance in Arabidopsis through improving the scavenging ability of reactive oxygen species. Additionally, an interaction between ScFAR1 and SsGTEL3a was identified, with ScFAR1 showing a positive response to drought stress in bacterium. In summary, this systematic analysis of GTE gene family in sugarcane and functional research of SsGTEL3a broadened deeper insight into their evolutionary dynamics and functional properties and provided new candidate genes for drought-resistant molecular breeding of sugarcane., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Understanding the water status of specific organs can be helpful in evaluating the life activities and growth conditions of maize. To accurately judge organ growth conditions and thus design appropriate interventions, it is necessary to clarify the true water dynamics of each maize organ. Using multiple maize cultivars with different growth periods, spatio-temporal water dynamics were analyzed here in the leaves, stalks, and ear components. Leaf water content was found to gradually decrease from both the bottom and top of the plant to the middle, whereas stalk water content decreased sequentially from the top to the bottom. Each successively higher node from the bottom of the plant was associated with decreases of 0.99% and 1.27% water content in the leaves and stalks, respectively. The water dynamics in leaves and internodes showed three clear stages: the slow loss, rapid loss, and balance stage. A water content of 60% appeared to be an irreversible turning point for initiation of senescence. Using normalized growth period as a measure, each of the tested cultivars could be assigned into one of two types based on their water dynamics: stay-water or general type. General-type cultivars had a shorter duration with a high water content and a water loss rate approximately twice as high as that of the stay-water type. This may have been related to the leaf senescence characteristics. However, the stay-water trait did not interfere with water dynamics of the ear components. Therefore, it may not be robust to evaluate the kernel dehydration of maize according to leaf senescence conditions due to the weak correlation between kernel water content and leaf senescence characteristics.

The growth of yield outputs is dwindling after the first green revolution, which cannot meet the demand for the projected population increase by the mid-century, especially with the constant threat from extreme climates. Cereal yield requires carbon (C) assimilation in the source for subsequent allocation and utilization in the sink. However, whether the source or sink limits yield improvement, a crucial question for strategic orientation in future breeding and cultivation, is still under debate. To narrow the knowledge gap and capture the progress, we focus on maize, rice, and wheat by briefly reviewing recent advances in yield improvement by modulation of i) leaf photosynthesis; ii) primary C allocation, phloem loading, and unloading; iii) C utilization and grain storage; and iv) systemic sugar signals (e.g., trehalose 6-phosphate). We highlight strategies for optimizing C allocation and utilization to coordinate the source-sink relationships and promote yields. Finally, based on the understanding of these physiological mechanisms, we envisage a future scenery of "smart crop" consisting of flexible coordination of plant C economy, with the goal of yield improvement and resilience in the field population of cereals crops., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BY declared a shared affiliation with the author ZG to the handling editor at the time of review., (Copyright © 2023 Liang, Gao, Fu, Chen, Shen and Zhou.)

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3-12 Hz) and encode an animal's position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30-100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

As an evolutionary strategy, plants overproduce ovaries as a safety net for survival, with those losing in the competition for resources being aborted. Grain abortion is, however, highly detrimental agronomically. The molecular basis of selective abortion of grain siblings remains unknown. In this opinion article we assess the current understanding of the molecular players controlling carbon resource import into ovaries and young grains, followed by an evaluation of the spatial hierarchy of sink capacity among grain siblings, focusing on the roles exerted by sugar transporters and enzymes. We argue that, upon sequential pollination and fertilization, robust activation of the carbon import and sugar signaling system plays a key role in establishing the capacity of grain siblings to acquire enough carbon resources to survive and thrive., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.

Rhythmic neural network activity has been broadly linked to behavior. However, it is unclear how membrane potentials of individual neurons track behavioral rhythms, even though many neurons exhibit pace-making properties in isolated brain circuits. To examine whether single-cell voltage rhythmicity is coupled to behavioral rhythms, we focused on delta-frequencies (1-4 Hz) that are known to occur at both the neural network and behavioral levels. We performed membrane voltage imaging of individual striatal neurons simultaneously with network-level local field potential recordings in mice during voluntary movement. We report sustained delta oscillations in the membrane potentials of many striatal neurons, particularly cholinergic interneurons, which organize spikes and network oscillations at beta-frequencies (20-40 Hz) associated with locomotion. Furthermore, the delta-frequency patterned cellular dynamics are coupled to animals' stepping cycles. Thus, delta-rhythmic cellular dynamics in cholinergic interneurons, known for their autonomous pace-making capabilities, play an important role in regulating network rhythmicity and movement patterning., (© 2023. The Author(s).)

Objective: To construct a kind of neural network for eliminating the metal artifacts in CT images by training the generative adversarial networks (GAN) model, so as to provide reference for clinical practice. Methods: The CT data of patients treated in the Department of Radiology, West China Hospital of Stomatology, Sichuan University from January 2017 to June 2022 were collected. A total of 1 000 cases of artifact-free CT data and 620 cases of metal artifact CT data were obtained, including 5 types of metal restorative materials, namely, fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies. Four hundred metal artifact CT data and 1 000 artifact-free CT data were utilized for simulation synthesis, and 1 000 pairs of simulated artifacts and metal images and simulated metal images (200 pairs of each type) were constructed. Under the condition that the data of the five metal artifacts were equal, the entire data set was randomly (computer random) divided into a training set (800 pairs) and a test set (200 pairs). The former was used to train the GAN model, and the latter was used to evaluate the performance of the GAN model. The test set was evaluated quantitatively and the quantitative indexes were root-mean-square error (RMSE) and structural similarity index measure (SSIM). The trained GAN model was employed to eliminate the metal artifacts from the CT data of the remaining 220 clinical cases of metal artifact CT data, and the elimination results were evaluated by two senior attending doctors using the modified LiKert scale. Results: The RMSE values for artifact elimination of fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies in test set were 0.018±0.004, 0.023±0.007, 0.015±0.003, 0.019±0.004, 0.024±0.008, respectively ( F= 1.29, P= 0.274). The SSIM values were 0.963±0.023, 0.961±0.023, 0.965±0.013, 0.958±0.022, 0.957±0.026, respectively ( F= 2.22, P= 0.069). The intra-group correlation coefficient of 2 evaluators was 0.972. For 220 clinical cases, the overall score of the modified LiKert scale was (3.73±1.13), indicating a satisfactory performance. The scores of modified LiKert scale for fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies were (3.68±1.13), (3.67±1.16), (3.97±1.03), (3.83±1.14), (3.33±1.12), respectively ( F= 1.44, P= 0.145). Conclusions: The metal artifact reduction GAN model constructed in this study can effectively remove the interference of metal artifacts and improve the image quality.

Purpose: Cataract is one of the leading causes of blindness worldwide, accounting for >50% of cases of blindness in low- and middle-income countries. In this study, two artificial intelligence (AI) diagnosis platforms are proposed for cortical cataract staging to achieve a precise diagnosis., Methods: A total of 647 high quality anterior segment images, which included the four stages of cataracts, were collected into the dataset. They were divided randomly into a training set and a test set using a stratified random-allocation technique at a ratio of 8:2. Then, after automatic or manual segmentation of the lens area of the cataract, the deep transform-learning (DTL) features extraction, PCA dimensionality reduction, multi-features fusion, fusion features selection, and classification models establishment, the automatic and manual segmentation DTL platforms were developed. Finally, the accuracy, confusion matrix, and area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the performance of the two platforms., Results: In the automatic segmentation DTL platform, the accuracy of the model in the training and test sets was 94.59 and 84.50%, respectively. In the manual segmentation DTL platform, the accuracy of the model in the training and test sets was 97.48 and 90.00%, respectively. In the test set, the micro and macro average AUCs of the two platforms reached >95% and the AUC for each classification was >90%. The results of a confusion matrix showed that all stages, except for mature, had a high recognition rate., Conclusion: Two AI diagnosis platforms were proposed for cortical cataract staging. The resulting automatic segmentation platform can stage cataracts more quickly, whereas the resulting manual segmentation platform can stage cataracts more accurately., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gan, Liu, Qin and Zhou.)

Importance: BRAF variants are associated with tumor progression; however, the prevalence of BRAF variant subtypes and their association with disease characteristics, prognosis, and targeted therapy response in patients with intrahepatic cholangiocarcinoma (ICC) are largely unknown., Objective: To explore the association of BRAF variant subtypes with disease characteristics, prognosis, and targeted therapy response in patients with ICC., Design, Setting, and Participants: In this cohort study, 1175 patients who underwent curative resection for ICC from January 1, 2009, through December 31, 2017, were evaluated at a single hospital in China. Whole-exome sequencing, targeted sequencing, and Sanger sequencing were performed to identify BRAF variants. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed using Cox proportional hazards regression. Associations between BRAF variants and targeted therapy response were tested in 6 BRAF-variant, patient-derived organoid lines and in 3 of the patient donors of those lines. Data were analyzed from June 1, 2021, to March 15, 2022., Interventions: Hepatectomy in patients with ICC., Main Outcomes and Measures: The association of BRAF variant subtypes with OS and DFS., Results: Of 1175 patients with ICC, the mean (SD) age was 59.4 (10.4) years and 701 (59.7%) were men. A total of 20 different subtypes of BRAF somatic variance affecting 49 patients (4.2%) were identified; V600E was the most frequent allele in this cohort, accounting for 27% of the identified BRAF variants, followed by K601E (14%), D594G (12%), and N581S (6%). Compared with patients with non-V600E BRAF variants, patients with BRAF V600E variants were more likely to have large tumor size (10 of 13 [77%] vs 12 of 36 [33%]; P = .007), multiple tumors (7 of 13 [54%] vs 8 of 36 [22%]; P = .04), and more vascular/bile duct invasion (7 of 13 [54%] vs 8 of 36 [22%]; P = .04). Multivariate analysis revealed that BRAF V600E variants, but not overall BRAF variants or non-V600E BRAF variants, were associated with poor OS (hazard ratio [HR], 1.87; 95% CI, 1.05-3.33; P = .03) and DFS (HR, 1.66; 95% CI, 1.03-2.97; P = .04). There were also broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors., Conclusions and Relevance: The findings of this cohort study suggest that there are broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Identifying and classifying BRAF variants may be able to help guide precise treatment for patients with ICC.

Objective: To explore the establishment and application of ovarian cancer organoids. Methods: Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50 ) in different organoids. Results: (1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t =3.429, P =0.022]. Conclusions: Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.

Background: This study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma., Methods: A total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What's more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis., Results: The patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable ( P <0.001). A clinical-pathological nomogram was constructed by combining clinical and pathological characteristics to predict the overall survival. In comparison with TNM stage, the concordance index and time-dependent receiver operating characteristic of the clinical-pathological nomogram showed better predictive value ( P <0.001). High quality of calibration plots in overall survival was noticed. As demonstrated by the decision curve analysis, the nomogram has better value than the TNM stage., Conclusions: As evidently revealed by the research findings, tumor-stroma ratio is an independent prognostic factor in patients with esophageal squamous cell carcinoma. The clinical-pathological nomogram has an incremental value compared TNM stage in predicting overall survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Song, Zhong, Zhao, Zhou, Xu, Li, Wang, Li, Wang, Lei, Wei, Wang, Fan, Han, Chen, Li, Ji, Yang, Li, Yang, Yang, Chang, Ren, Zhou and Wang.)

In the North China Plain, the excessive application of nitrogen (N) fertilizer for ensuring high yield and a single application at sowing for simplifying management in farmer practice lead to low N use efficiency and environmental risk in maize ( Zea mays L.) production. However, it is unclear whether and how late split application with a lower level of N fertilizer influences maize yield. To address this question, a two-year field experiment was conducted with two commercial maize cultivars (Zhengdan 958 and Denghai 605) using a lower level of N input (180 kg ha -1 ) by setting up single application at sowing and split application at sowing and later stages (V12, R1, and R2) with four different ratios, respectively. The maize yield with split-applied 180 kg ha -1 N did not decrease compared to the average yield with 240 kg ha -1 N input in farmer practice, while it increased by 6.7% to 11.5% in the four N split-application treatments compared with that of the single-application control. Morphological and physiological analyses demonstrated that late split application of N (i) increased the net photosynthetic rate and chlorophyll content and thus promoted the photosynthetic efficiency during the reproductive stages; (ii) promoted the sink capacity via improved kernel number, endosperm cells division, and grain-filling rate; and (iii) increased the final N content and N efficiency in the plant. Therefore, we propose that late split application of N could reduce N fertilizer input and coordinately improve N efficiency and grain yield in summer maize production, which are likely achieved by optimizing the source-sink relations during the grain-filling stage.

Despite improvement in cardiopulmonary resuscitation (CPR) performance, cardiac arrest (CA) is still associated with poor prognosis. The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury (I/R). The guidelines for CPR suggest the use of therapeutic hypothermia (TH) as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury. During TH, sedative agents (propofol) and analgesia agents (fentanyl) are commonly used to prevent shiver and pain. However, propofol has been associated with a number of serious adverse effects such as metabolic acidosis, cardiac asystole, myocardial failure, and death. In addition, mild TH alters the pharmacokinetics of agents (propofol and fentanyl) and reduces their systemic clearance. For CA patients undergoing TH, propofol can be overdosed, leading to delayed awakening, prolonged mechanical ventilation, and other subsequent complications. Ciprofol (HSK3486) is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room. Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol. Therefore, we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs., Competing Interests: Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Protective effects of combined treatment with Ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury”., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: This study aims to explore the application value of computed tomography (CT) three-dimensional (3D) reconstruction, magnetic resonance imaging (MRI) 3D reconstruction, and conventional digital subtraction angiography (DSA) fluoroscopy in percutaneous transhepatic cholangial drainage (PTCD)., Methods: The clinical data of 180 patients with obstructive jaundice requiring PTCD from December 2017 to December 2021 were retrospectively analyzed. Following PTCD, CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy were conducted, after which the surgical success rates, liver function results, and postsurgical complications were compared., Results: The puncture accuracies under CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy were 90.0% (54/60), 96.7% (58/60), and 80% (48/60), respectively. The degree of jaundice and epigastric discomfort was relieved in all three groups after surgery, while a significant reduction in the levels of total bilirubin and direct bilirubin was observed relative to the levels before surgery ( P  < 0.05). The incidences of complications in the CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy groups were 6.7% (4/60), 3.3% (2/60), and 13.3% (8/60), respectively, and the differences among the three groups were statistically significant ( P  < 0.05)., Conclusion: Conducting conventional enhanced CT and MRI scans in patients before surgery might be more practical than the conventional puncture method. Among the methods under study, MRI 3D reconstruction was found to be safer and more feasible than CT 3D reconstruction and conventional DSA fluoroscopy in PTCD. MRI 3D reconstruction could reduce the degree of jaundice, improve the success rate of surgery, reduce the incidence of complications due to surgery, and improve the patients' tolerance to surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhou, Ji, Zhou, Xu, Xin and Huang.)

Objective: Two classes of spiro[4 H -pyran-3,3'-oxindole] derivatives were prepared via the one pot reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins and malononitrile successfully catalyzed by a Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1 H -pyrazol [b,f ][4,5]-1,5-diazadicyclo[3.3.1]-2,6-octadiene). The antibacterial activity of products against three wild-type bacteria ( B. subtilis, S. aureus , and E. coli) and two resistant strains (Methicillin-resistant S. aureus (18H 8 ) and E. coli carrying the BlaNDM-1 gene (18H 5 )) was evaluated using the minimum inhibitory concentration (MIC).., Methods: 1-Phenyl-1,3-butanedione 2 or dibenzoylmethane 2' (0.42 mmol), substituted isatin 3 (0.4 mmol), malononitrile 4 (0.8 mmol), Tröger's base derivative 1b (0.08 mmol), and 10 mL of acetonitrile were added to a 50 mL round bottom flask and refluxed. After the completion (TLC monitoring), water (10 mL) was added to the reaction mixture; pH = 7 was adjusted with saturated NaHCO 3 (aq.), and the mixture was extracted with CH 2 Cl 2 (50 mL × 3). Organic layers were combined and dried with anhydrous Na 2 SO 4 ; the solvent was removed under vacuum, and the residue was purified by column chromatography (V DCM : V MeOH = 80: 1) to afford product 5. The antibacterial activity was tested by the MTT method., Results: Seventeen spiro[4 H -pyran-3,3'-oxindole] derivatives were synthesized through the reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot in medium to high yields. Four compounds showed antibacterial activity, and two of them showed the same activity as the positive control Ceftazidime on S. aureus (MIC = 12.5 μg/mL)., Conclusion: Two classes of spiro[4 H -pyran-3,3'-oxindole] derivatives were prepared, and their antibacterial activity was evaluated. Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1 H -pyrazol[ b,f ][4,5]- 1,5-diazadicyclo[3,3,1]-2,6-octadiene) was used as an efficient organocatalyst for the reaction of low reactive chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot successfully and effectively by providing multiple active sites and alkaline environment. By the theoretical calculation, we explained the possible reaction sequence and mechanism. Due to the superiority and high efficiency of the TB framework as an organocatalyst, the reaction showed many advantages, including mild reaction conditions, low catalyst loading, and a wide substrate range. It expanded the application of Tröger's base to the multicomponent reaction in organocatalysis. Some products were screened due to their high antibacterial activity in vitro , showing their potential in new antibacterial drug development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)