Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

Trace Selenium Doping for Improving the Reaction Kinetics of ZnS Cathode for Aqueous Zn-S Batteries.

Aqueous Zinc-sulfur (Zn-S) batteries are promising for the field of energy storage due to their low cost, high theoretical capacity, and safety. However, the large volume expansion and the inherently poor conductivity of sulfur would result in electrode cracking and sluggish reaction kinetics, limiting the practical application of Zn-S batteries. Herein, commercial zinc sulfide (ZnS) is employed instead of S as cathode and proposed a doping modification strategy to solve the above problems. The designed ZnS0.93Se0.07 cathode shows good cycle stability and much-improved reaction kinetics, which is due to the smaller bandgap of ZnS0.93Se0.07 (1.40 eV) compared to ZnS (1.86 eV). As a result, the obtained ZnS0.93Se0.07 cathode exhibits a high specific capacity of 552 mAh g-1 (1672.6 mAh g-1 based on S) at 0.1 A g-1 and 330 mAh g-1 (1000 mAh g-1 based on S) at 2 A g-1. Moreover, the ZnS0.93Se0.07 cathode can provide a high areal capacity of 3.8 mAh cm-2 at a high mass loading of 10 mg cm-2 and limited electrolyte (4 µL mg-1). This work provides a simple and effective cathode modification strategy, which is conducive to promoting the practical application of Zn-S batteries.

Practical Prediction of New Baseline Renal Function After Partial Nephrectomy.

BACKGROUND: Partial nephrectomy (PN) is generally preferred for localized renal masses due to strong functional outcomes. Accurate prediction of new baseline glomerular filtration rate (NBGFR) after PN may facilitate preoperative counseling because NBGFR may affect long-term survival, particularly for patients with preoperative chronic kidney disease. Methods for predicting parenchymal volume preservation, and by extension NBGFR, have been proposed, including those based on contact surface area (CSA) or direct measurement of tissue likely to be excised/devascularized during PN. We previously reported that presuming 89% of global GFR preservation (the median value saved from previous, independent analyses) is as accurate as the more subjective/labor-intensive CSA and direct measurement approaches. More recently, several promising complex/multivariable predictive algorithms have been published, which typically include tumor, patient, and surgical factors. In this study, we compare our conceptually simple approach (NBGFRPost-PN = 0.90 × GFRPre-PN) with these sophisticated algorithms, presuming that an even 90% of the global GFR is saved with each PN. PATIENTS AND METHODS: A total of 631 patients with bilateral kidneys who underwent PN at Cleveland Clinic (2012-2014) for localized renal masses with available preoperative/postoperative GFR were analyzed. NBGFR was defined as the final GFR 3-12 months post-PN. Predictive accuracies were assessed from correlation coefficients (r) and mean squared errors (MSE). RESULTS: Our conceptually simple approach based on uniform 90% functional preservation had equivalent r values when compared with complex, multivariable models, and had the lowest degree of error when predicting NBGFR post-PN. CONCLUSIONS: Our simple formula performs equally well as complex algorithms when predicting NBGFR after PN. Strong anchoring by preoperative GFR and minimal functional loss (≈ 10%) with the typical PN likely account for these observations. This formula is practical and can facilitate counseling about expected postoperative functional outcomes after PN.

Thermal Ablation Versus Partial Nephrectomy for cT1 Renal Mass in a Solitary Kidney: A Matched Cohort Comparative Analysis.

BACKGROUND: Nephron-sparing approaches are preferred for renal mass in a solitary kidney (RMSK), with partial nephrectomy (PN) generally prioritized. Thermal ablation (TA) also is an option for small renal masses in this setting; however, comparative functional/survival outcomes are not well-defined. METHODS: A retrospective study of 504 patients (1975-2022) with cT1 RMSK managed with PN (n = 409)/TA (n = 95) with necessary data for analysis was performed. Propensity score was used for matching patients, including age, preoperative glomerular filtration rate (GFR), tumor diameter, R.E.N.A.L. ((R)adius (tumor size as maximal diameter), (E)xophytic/endophytic properties of tumor, (N)earness of tumor deepest portion to collecting system or sinus, (A)nterior (a)/posterior (p) descriptor, and (L)ocation relative to polar lines), and comorbidities. Functional outcomes were compared, and Kaplan-Meier was used to analyze survival. RESULTS: The matched cohort included 132 patients (TA = 66/PN = 66), with median tumor diameter of 2.4 cm, R.E.N.A.L. of 6, and preoperative GFR of 52 ml/min/1.73 m2. Acute kidney injury occurred in 11%/61% in the TA/PN cohorts, respectively (p < 0.01). After recovery, median GFR preserved was 89%/83% for TA/PN, respectively (p = 0.02), and 5-year dialysis-free survival was 96% in both cohorts. Median follow-up was 53 months. Five-year recurrence-free survival (RFS) was 62%/86% in the TA/PN cohorts, respectively (p < 0.01). Five-year local recurrence (LR)-free survival was 74%/95% in the TA/PN cohorts, respectively (p < 0.01). Five-year cancer-specific survival (CSS) was 96%/98% in the TA/PN cohorts, respectively (p = 0.7). Local recurrence was observed in nine of 36 (25%) and five of 30 (17%) patients managed with laparoscopic versus percutaneous TA, respectively. For TA with LR (n = 14), nine patients presented with multifocality and/or cT1b tumors. Twelve LR were managed with salvage TA, and seven remained cancer-free, while five developed systemic recurrence, three with concomitant LR. CONCLUSIONS: Functional outcomes for TA for RMSK were improved compared with PN. Local recurrence was more common after TA and often was associated with the laparoscopic approach, multifocality, and large tumor size. Improved patient selection and greater experience with TA should improve outcomes. Salvage of LR was not always possible. Partial nephrectomy remains the reference standard for RMSK.

Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

NMNATs expression inhibition mediated NAD+ deficiency plays a critical role in doxorubicin-induced hepatotoxicity in mice.

Doxorubicin (DOX) is one of the most widely used antineoplastic drugs with known cardiotoxicity while other organ toxicity, such as hepatotoxicity is not well defined. This study was to explore the role of nicotinamide adenine dinucleotide (NAD+) in DOX-induced hepatotoxicity. DOX (20 mg/kg) induced acute liver injury and oxidative stress in C57BL/6 J mice at 48 h. Notably, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H dehydrogenase quinone 1 (NQO1) were downregulated. NAD+ deficiency was confirmed due to DOX exposure. Mechanistically, the downregulation of nicotinamide mononucleotide adenylyl transferase 1 (NMNAT1), NMNAT2 and NMNAT3, while no alteration of nicotinamide phosphoribosyl transferase was proved. As a consequence of NAD+ deficiency, the expression of poly-ADP-ribose polymerase1 (PARP1), CD38 and Sirtuin1 (SIRT1) were reduced. Furthermore, supplementation of NAD+ (200 mg/kg/day) or its precursor nicotinamide mononucleotide (NMN) (500 mg/kg/day) alleviated liver injury, attenuated oxidative stress, and elevated the downregulation of Nrf2 and NQO1. More importantly, compromised expression of NMNAT1-3, PARP1, CD38 and SIRT1 were improved by NAD+ and NMN. In conclusion, NAD+ deficiency due to NMNATs expression inhibition may attribute to the pathogenesis of DOX-induced hepatotoxicity, thus providing new insights for mitigating DOX side effects.

Parenchymal volume preservation during partial nephrectomy: improved methodology to assess impact and predictive factors.

OBJECTIVE: To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia) on functional outcomes after partial nephrectomy (PN) using an accurate and objective software-based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP. PATIENTS AND METHODS: A total of 894 PN patients with available studies (2011-2014) were evaluated. The PPVP was measured from cross-sectional imaging at ≤3 months before and 3-12 months after PN using semi-automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative-importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP. RESULTS: The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2, and the median (interquartile range [IQR]) percentage of ipsilateral GFR preserved was 80% (71-88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76-92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05). CONCLUSIONS: A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour-related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys.

Nirmatrelvir and ritonavir for inpatients with severe or critical COVID-19 beyond five days of symptom onset: a propensity score-matched, multicenter, retrospective cohort study.

BACKGROUND: There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient. METHODS: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated. RESULTS: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited. CONCLUSIONS: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

Correlation of serum Meteorin-like (Metrnl) level with type 2 diabetic peripheral neuropathy.

OBJECTIVE: Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the Metrnl level and diabetic peripheral neuropathy (DPN). METHODS: The investigation was conducted on a sample of 80 patients with type 2 diabetes mellitus (T2DM) and 60 healthy controls. The T2DM patients were categorized into two subgroups based on skin biopsy: the DPN subgroup (n = 20) and the diabetes without neuropathy subgroup (n = 60). RESULTS: The T2DM groups had higher serum Metrnl concentrations compared with the controls. The serum Metrnl concentration was significantly lower in the DPN group than in T2DM patients without neuropathy. Logistic regression analysis demonstrated a notable correlation between serum Metrnl and DPN (OR: 0.997, 95% CI: 0.995-1.000, P < 0.05). Serum Metrnl level was negatively correlated with age and SBP after a simple logistic regression analysis. CONCLUSION: Serum Metrnl concentration is independently correlated with DPN.

Corticosteroid in IgA nephropathy with moderate proteinuria: A retrospective cohort study.

BACKGROUND: Corticosteroids remain contentious as a therapeutic option for IgA nephropathy. We conducted a retrospective cohort study to explore whether corticosteroid therapy is efficient and safe for IgAN patients with moderate proteinuria. METHODS: A total of 336 patients with renal biopsy-confirmed IgAN, estimated glomerular filtration (eGFR) over 15 mL/min/1.73 m2 and urine protein levels of 0.75-3.5 g/d were enrolled. According to the treatment protocol, we classified the enrolled patients into two groups: one receiving corticosteroids and the other receiving supportive care. Complete remission, partial remission, and no remission were applied to describe the efficacy assessments. The endpoint was defined as a 40% reduction in eGFR, the onset of ESRD, or renal disease-related death. RESULTS: Clinical and pathological progression risk factors were higher in corticosteroid-treated individuals. Logistic regression analysis revealed that the corticosteroid group was considerably related to a higher remission rate after adjustment for confounding factors. The occurrence of serious adverse events between the two groups was not found to be statistically significantly different. Then, we matched 95 couples of patients with similar baseline levels in both groups by propensity score matching. The results showed that corticosteroid-treated patients showed higher overall and complete remission rates than untreated patients. However, due to the relatively short follow-up period, no significant differences in the incidence of endpoint and survival analyses have been observed thus far. CONCLUSION: Corticosteroid therapy may benefit IgAN patients with moderate proteinuria via proteinuria reduction and renal function preservation.

Temperature-induced embryonic diapause in chickens is mediated by PKC-NF-κB-IRF1 signaling.

BACKGROUND: Embryonic diapause (dormancy) is a state of temporary arrest of embryonic development that is triggered by unfavorable conditions and serves as an evolutionary strategy to ensure reproductive survival. Unlike maternally-controlled embryonic diapause in mammals, chicken embryonic diapause is critically dependent on the environmental temperature. However, the molecular control of diapause in avian species remains largely uncharacterized. In this study, we evaluated the dynamic transcriptomic and phosphoproteomic profiles of chicken embryos in pre-diapause, diapause, and reactivated states. RESULTS: Our data demonstrated a characteristic gene expression pattern in effects on cell survival-associated and stress response signaling pathways. Unlike mammalian diapause, mTOR signaling is not responsible for chicken diapause. However, cold stress responsive genes, such as IRF1, were identified as key regulators of diapause. Further in vitro investigation showed that cold stress-induced transcription of IRF1 was dependent on the PKC-NF-κB signaling pathway, providing a mechanism for proliferation arrest during diapause. Consistently, in vivo overexpression of IRF1 in diapause embryos blocked reactivation after restoration of developmental temperatures. CONCLUSIONS: We concluded that embryonic diapause in chicken is characterized by proliferation arrest, which is the same with other spices. However, chicken embryonic diapause is strictly correlated with the cold stress signal and mediated by PKC-NF-κB-IRF1 signaling, which distinguish chicken diapause from the mTOR based diapause in mammals.

A case of death after the severing three appendiceal arteries during appendectomy.

INTRODUCTION: Acute appendicitis is one of the most common acute abdominal issues requiring surgery and is usually treated by appendectomy. During the process of removing the appendix, the appendiceal artery is severed. In most individuals, the appendix is supplied by only one appendiceal artery. CASE PRESENTATION: A 50-year-old man underwent appendectomy. During the surgical procedure, the appendix artery and two accessory arteries of the appendix were severed, leading to massive hemorrhaging in the abdominal cavity, which ultimately resulted in the patient's unfortunate demise. CONCLUSION: Through this case, we hope that surgeons can learn more about the anatomy of the appendiceal artery and understand the possibility of accessory arteries to the appendix. During surgery, the blood vessels supplying the appendix should be carefully explored, and the "one-size-fits-all approach" should be avoided. Moreover, attention should be given to complications after appendectomy, and timely symptomatic treatment should be provided. Key points 1. Rare typing: The case of death due to improper handling of the accessory appendicular artery during appendectomy in patients with three appendiceal arteries is currently unreported. 2. Detailed anatomical knowledge: Surgeons performing an appendectomy need to make a detailed exploration of the blood vessel supply of the appendix to avoid ignoring anatomically different blood vessels. 3. Avoid a one-size-fits-all approach: In the surgical process, a "one-size-fits-all" approach should be avoided, that is, the same surgical approach should not be used in all cases, but should be adjusted according to the anatomical characteristics of the individual. 4. Observation of postoperative bleeding: In the perioperative period, peritoneal drainage should be closely observed. If a large amount of bloody fluid is found, timely surgical treatment should be carried out. 5. Attention to complications: Surgeons should pay.

The phosphoproteomic and interactomic landscape of qGL3/OsPPKL1-mediated brassinosteroid signaling in rice.

Oryza sativa L. (rice) is one of the most important crops in the world, and grain size is a major component determining rice yield. Recent studies have identified a number of grain size regulators, which are involved in phytohormone signaling, G protein signaling, the mitogen-activated protein kinase signaling pathway, the ubiquitin-proteasome pathway or transcriptional regulation. In a previous study, we cloned qGL3/OsPPKL1 encoding a rice protein phosphatase that negatively modulates brassinosteroid (BR) signaling and grain length. Here, to further explore the qGL3-mediated BR signaling network, we performed phosphoproteomic screenings using two pairs of rice materials: the indica rice cultivar 9311 and its near-isogenic line NILqgl3 and the japonica rice cultivar Dongjin and its qGL3 knockout mutant m-qgl3. Together with qGL3-interacting proteins, we constructed the qGL3-mediated network, which reveals the relationships between BR signaling and other critical signaling pathways. Transgenic plants of these network components showed BR-related alterations in plant architecture. From this network, we validated a qGL3-interacting protein, O. sativa VERNALIZATION INSENSITIVE 3-LIKE 1 (OsVIL1), and demonstrated that qGL3 dephosphorylates OsVIL1 to modulate BR signaling. The qGL3-dependent network uncovered in this study increases our understanding of BR signaling and provides a profound foundation for addressing how BR modulates plant architecture in rice.

Oriented Zinc Metal Anode Based on Directional Recognition and Assembly.

The practical application of aqueous zinc batteries are highly limited by unsatisfied Zn anodes for the unavoidable dendrite growth and side reactions. Crystal orientation engineering is an effective way to overcome these inherent drawbacks. However, how to achieve Zn plating with manipulated crystallographic orientation is still a great challenge. Herein, a uniform (002)-oriented Zn metal anode is reported based on a directional cation recognition and crystal assembly strategy. The activated layered double hydroxide (Act-LDH) exhibits favorable adsorption energy with Zn2+ and high lattice matching with Zn (002) plane, which can be served as directional recognition layer to anchor Zn2+ and regulate crystallographic orientation of Zn as well. As demonstration, Zn crystals with ultrahigh ratio of (002)/(100) plane of 15.7 are assembled parallelly on horizontal Act-LDH, in which high CE of 99.85% maintains over 18 000 cycles. The symmetric battery with (002)-oriented Zn shows stable plating/stripping process over 1650 and 420 h at 1 mA cm-2 /0.5 mA h cm-2 and 10 mA cm-2 /5 mA h cm-2 , respectively, which is 9 and 12 times higher than unoriented polycrystalline Zn. Moreover, as-assembled full battery displays high specific capacity of 120 mA h g-1 at 2 A g-1 over 1800 cycles.

Enhancing the Initial Coulombic Efficiency of Sodium-Ion Batteries via Highly Active Na2 S as Presodiation Additive.

Recently, sodium-ion batteries (SIBs) have received considerable attention for large-scale energy storage applications. However, the low initial Coulombic efficiency of traditional SIBs severely impedes their further development. Here, a highly active Na2 S-based composite is employed as a self-sacrificial additive for sodium compensation in SIBs. The in situ synthesized Na2 S is wrapped in a carbon matrix with nanoscale particle size and good electrical conductivity, which helps it to achieve a significantly enhanced electrochemical activity as compare to commercial Na2 S. As a highly efficient presodiation additive, the proposed Na2 S/C composite can reach an initial charge capacity of 407 mAh g-1 . When 10 wt.% Na2 S/C additive is dispersed in the Na3 V2 (PO4 )3 cathode, and combined with a hard carbon anode, the full cell achieves 24.3% higher first discharge capacity, which corresponds to a 18.3% increase in the energy density from 117.2 to 138.6 Wh kg-1 . Meanwhile, it is found that the Na2 S additive does not generate additional gas during the initial charging process, and under an appropriate content, its reaction product has no adverse impact on the cycling stability and rate performance of SIBs. Overall, this work establishes Na2 S as a highly effective additive for the construction of advanced high-energy-density SIBs.

qGL3/OsPPKL1 induces phosphorylation of 14-3-3 protein OsGF14b to inhibit OsBZR1 function in brassinosteroid signaling.

Brassinosteroids (BRs) play essential roles in regulating plant growth and development, however, gaps still remain in our understanding of the BR signaling network. We previously cloned a grain length quantitative trait locus qGL3, encoding a rice (Oryza sativa L.) protein phosphatase with Kelch-like repeat domain (OsPPKL1), that negatively regulates grain length and BR signaling. To further explore the BR signaling network, we performed phosphoproteomic analysis to screen qGL3-regulated downstream components. We selected a 14-3-3 protein OsGF14b from the phosphoproteomic data for further analysis. qGL3 promoted the phosphorylation of OsGF14b and induced the interaction intensity between OsGF14b and OsBZR1. In addition, phosphorylation of OsGF14b played an important role in regulating nucleocytoplasmic shuttling of OsBZR1. The serine acids (Ser258Ser259) residues of OsGF14b play an essential role in BR-mediated responses and plant development. Genetic and molecular analyses indicated that OsGF14b functions as a negative regulator in BR signaling and represses the transcriptional activation activity of OsBZR1. Collectively, these results demonstrate that qGL3 induces the phosphorylation of OsGF14b, which modulates nucleocytoplasmic shuttling and transcriptional activation activity of OsBZR1, to eventually negatively regulate BR signaling and grain length in rice.

Optical bistability modulation based on graphene sandwich structure with topological interface modes.

In this paper, we have investigated optical bistability modulation of transmitted beam that can be achieved by graphene sandwich structure with topological interface modes at terahertz frequency. Graphene with strong nonlinear optical effect was combined with sandwich photonic crystal to form a new sandwich structure with topological interface modes. The light-limiting properties of the topological interface modes, as well as its high unidirectionality and high transmission efficiency, all contribute positively to the reduction of the optical bistability threshold. In addition, the topological interface modes can effectively ensure the stability of the two steady state switching in the case of external interference. Moreover, optical bistability is closely related to the incident angle, the Fermi energy, the relaxation time, and the number of layers of graphene. Through parameter optimization, optical bistability with threshold of 105 V/m can be obtained, which has reached or is close to the range of the weak field.

Optical bistability in a heterodimer composed of a quantum dot and a metallic nanoshell.

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

OsBAK2/OsSERK2 expression is repressed by OsBZR1 to modulate brassinosteroid response and grain length in rice.

Brassinosteroids (BRs) are a class of polyhydroxylated steroidal phytohormones that are essential for plant growth and development. Rice BRASSINOSTEROID-INSENSITIVE1 (BRI1)-ASSOCIATED RECEPTOR KINASES (OsBAKs) are plasma membrane-localized receptor kinases belonging to the subfamily of leucine-rich repeat receptor kinases. It has been found that in Arabidopsis, BRs induce the formation of a BRI1-BAK1 heterodimer complex and transmit the cascade signal to BRASSINAZOLE RESISTANT1/bri1-EMS-SUPPRESSOR1 (BZR1/BES1) to regulate BR signaling. Here, in rice (Oryza sativa ssp. japonica), we found that OsBZR1 binds directly to the promoter of OsBAK2, but not OsBAK1, and represses the expression of OsBAK2 to form a BR feedback inhibition loop. Additionally, the phosphorylation of OsBZR1 by OsGSK3 reduced its binding to the OsBAK2 promoter. The osbak2 mutant displays a typical BR-deficiency phenotype and negative modulates the accumulation of OsBZR1. Interestingly, the grain length of the osbak2 mutant was increased whereas in the cr-osbak2/cr-osbzr1 double mutant, the reduced grain length of the cr-osbzr1 mutant was restored, implying that the increased grain length of osbak2 may be due to the rice somatic embryogenesis receptor kinase-dependent pathway. Our study reveals a novel mechanism by which OsBAK2 and OsBZR1 engage in a negative feedback loop to maintain rice BR homeostasis, facilitating a deeper understanding of the BR signaling network and grain length regulation in rice.

Two machine learning-based nomogram to predict risk and prognostic factors for liver metastasis from pancreatic neuroendocrine tumors: a multicenter study.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are one of the most common endocrine tumors, and liver metastasis (LMs) are the most common location of metastasis from PNETS; However, there is no valid nomogram to predict the diagnosis and prognosis of liver metastasis (LMs) from PNETs. Therefore, we aimed to develop a valid predictive model to aid physicians in making better clinical decisions. METHODS: We screened patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2016. Feature selection was performed by machine learning algorithms and then models were constructed. Two nomograms were constructed based on the feature selection algorithm to predict the prognosis and risk of LMs from PNETs. We then used the area under the curve (AUC), receiver operating characteristic (ROC) curve, calibration plot and consistency index (C-index) to evaluate the discrimination and accuracy of the nomograms. Kaplan-Meier (K-M) survival curves and decision curve analysis (DCA) were also used further to validate the clinical efficacy of the nomograms. In the external validation set, the same validation is performed. RESULTS: Of the 1998 patients screened from the SEER database with a pathological diagnosis of PNET, 343 (17.2%) had LMs at the time of diagnosis. The independent risk factors for the occurrence of LMs in PNET patients included histological grade, N stage, surgery, chemotherapy, tumor size and bone metastasis. According to Cox regression analysis, we found that histological subtype, histological grade, surgery, age, and brain metastasis were independent prognostic factors for PNET patients with LMs. Based on these factors, the two nomograms demonstrated good performance in model evaluation. CONCLUSION: We developed two clinically significant predictive models to aid physicians in personalized clinical decision-makings.