Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic lipid accumulation, which can progress to nonalcoholic steatohepatitis (NASH). Histone deacetylase Sirtuin 6 (SIRT6) regulates NAFLD by regulating metabolism-related gene expression, but an extrachromosomal role for SIRT6 in NAFLD development remains elusive. We investigated whether SIRT6 functions on NAFLD in the cytoplasm. We found that SIRT6 binds saturated fatty acids, especially palmitic acid. This binding leads to its nuclear export, where it deacetylates long-chain acyl-CoA synthase 5 (ACSL5), thereby facilitating fatty acid oxidation. High-fat diet-induced NAFLD is suppressed by ACSL5 hepatic overexpression but is exacerbated by its depletion. As confirmation, overexpression of a deacetylated ACSL5 mimic attenuated NAFLD in Sirt6 liver-specific knockout mice. Moreover, NASH-hepatic tissues from both patients and diet-fed mice exhibited significantly reduced cytoplasmic SIRT6 levels and increased ACSL5 acetylation. The SIRT6/ACSL5 signaling pathway has a critical role in NAFLD progression and might constitute an avenue for therapeutic intervention.

A Study to Analyse the Feasibility and Effectiveness of Left Bundle Branch Area Pacing Used in Young Children.

This study aimed to investigate the feasibility and effectiveness of left bundle branch area pacing (LBBaP) in young children. From September 2020 to May 2021, a total of 31 children (≤ 7 years) with complete atrioventricular block were included. All patients were scheduled to undergo LBBaP. Pacing parameters, and cardiac function and synchrony were evaluated during follow-up. LBBaP succeeded in 21 children (3.3 ± 2.1 years old), with a success rate of 70.9%. LBBaP failed in nine children, who eventually received right ventricular septal pacing (RVSP). The average postoperative QRS duration in patients of LBBaP group was narrower than that of RVSP group: 100.9 ± 9.1 versus 114.2 ± 11.9 ms (P = 0.002). The median follow-up duration was 12 [interquartile range (IQR) 6-15] months. At last time of follow-up, the capture threshold of ventricular electrode in patients of LBBaP group were significantly lower than that of RVSP group (0.70 ± 0.25 versus 1.39 ± 0.94 V, P = 0.011). The echo-left ventricular ejection fraction (LVEF) in patients in the LBBaP group was better than that in the RVSP group (66.1 ± 3.3 versus 63.1 ± 2.2%, P = 0.025). LBBaP can be safely and effectively administered in young children. Satisfactory pacing parameters, and narrow QRS durations were obtained.

Evaluation of a rail logistics transmission system for the transportation of blood components within a medical centre.

BACKGROUND AND OBJECTIVES: Rail logistics transmission systems (RLTSs) are commonly used for the transportation of blood samples, pathological specimens and other medical materials in many hospitals, as they are rapid, secure, cost-effective and intelligent. However, few studies have evaluated blood component transportation from blood banks to the patient care areas of hospitals using RLTS. In this study, we evaluate the RLTS used for the transportation of blood components within a medical centre. MATERIALS AND METHODS: The dispatch of blood components, including packed red blood cells (pRBCs), fresh frozen plasma (FFP), cryoprecipitate and platelet units, from a blood bank to critical care areas or general wards was done using RLTS. Parameters such as the delivery time, temperature, physical integrity and blood component quality were evaluated via analytical testing using specimens obtained before and after transportation by RLTS. RESULTS: The turnaround time and temperature of all tested blood units via RLTS transportation were able to meet the clinical demands of blood component delivery (median time: 323 s [118-668 s]; temperature variation: 4.5-8.9°C for pRBCs and FFP and 21.5-23.5°C for cryoprecipitate and platelet units). Furthermore, parameters of pRBC quality, including the haemolysis index and potassium and lactate dehydrogenase levels in plasma, were not significantly different before and after transportation through RLTS. Similarly, RLTS transportation affected neither the basic coagulation test results in FFP and cryoprecipitate specimens nor platelet aggregation and activation markers in apheresis platelet specimens. CONCLUSION: Hospital-wide delivery of blood components via RLTS seems to be safe, reliable and cost-effective and does not have any negative impact on blood quality. Therefore, the establishment of standard criteria, protocols and guidelines based on further studies is needed.

Left ventricular pacing in the treatment of pediatric cardiac dysfunction caused by idiopathic complete left bundle branch block.

OBJECTIVE: This study aimed to investigate the feasibility and effectiveness of transthoracic epicardial dual-chamber pacemaker implantation in the treatment of cardiac dysfunction caused by idiopathic complete left bundle branch block (CLBBB) in children. METHODS: Nine children diagnosed with cardiac dysfunction due to idiopathic CLBBB were included in this study. All patients underwent transthoracic epicardial dual-chamber pacemaker implantation. Cardiac function was evaluated using echocardiography during the follow-up. Additionally, intraventricular synchronization parameters were assessed using two-dimensional speckle tracking echocardiography (STE). RESULTS: Nine children (mean age, 3.0 ± 2.6 years) were included in this study. The median follow-up duration was 2 (interquartile range, 1-3) years. The cardiac function of all patients recovered to normal levels within 1 year postoperatively. The postoperative QRS duration on electrocardiography (142 ± 21 ms) was significantly shorter than that at baseline (106 ± 12 ms) (p < .05). Cardiac dyssynchrony in patients who manifested preoperatively achieved complete correction after pacemaker implantation. The comparison of preoperative and postoperative (last follow-up visit) synchronization parameters were as follows: longitudinal standard deviation of the time to peak strain, 99.0 ± 41.9 versus 36.8 ± 5.0 ms (p = .004); delay time of peak longitudinal strain, 252.2 ± 131.4 versus 35.0 ± 22.9 ms (p = .002); and longitudinal systolic dyssynchrony index, 2.8 ± 0.8% versus 1.0 ± 0.3% (p = .001), respectively. CONCLUSION: Transthoracic epicardial dual-chamber pacemaker implantation (with left atrial sensing and left ventricular single-site pacing) can be used for the treatment of cardiac dysfunction caused by idiopathic CLBBB in children.

Analysis of the influencing factors associated with dyssynchrony and cardiac dysfunction in children with ventricular pre-excitation.

OBJECTIVE: To investigate the correlation between ventricular pre-excitation-related dyssynchrony, on cardiac dysfunction, and recovery. METHODS AND RESULTS: This study included 76 children (39 boys and 37 girls) with a median age of 5.25 (2.67-10.75) years. The patients with pre-excitation-related cardiac dysfunction (cardiac dysfunction group, n = 34) had a longer standard deviation of the time-to-peak systolic strain of the left ventricle and larger difference between the maximum and minimum times-to-peak systolic strain than those with a normal cardiac function (normal function group, n = 42) (51.77 ± 24.70 ms versus 33.29 ± 9.48 ms, p < 0.05; 185.82 ± 92.51 ms versus 111.93 ± 34.27 ms, p < 0.05, respectively). The cardiac dysfunction group had a maximum time-to-peak systolic strain at the basal segments of the anterior and posterior septa and the normal function group at the basal segments of anterolateral and posterolateral walls. The prevalence of ventricular septal dyssynchrony in the cardiac dysfunction group was significantly higher than that in the normal function group (94.1% (32/34) versus 7.7% (3/42), p < 0.05). The patients with ventricular septal dyssynchrony (n = 35) had a significantly higher prevalence of intra-left ventricular systolic dyssynchrony than those with ventricular septal synchrony (n = 41) (57.1% (20/35) versus 14.6% (6/41), p < 0.05). During follow-up after pathway ablation, the patients who recovered from intra-left ventricular dyssynchrony (n = 29) had a shorter left ventricular ejection fraction recovery time than those who did not (n = 5) (χ2 = 5.94, p < 0.05). Among the patients who recovered, 93.1% (27/29) had a normalised standard deviation of the time-to-peak systolic strain and difference between the maximum and minimum times-to-peak systolic strain within 1 month after ablation. CONCLUSION: Ventricular pre-excitation may cause ventricular septal dyssynchrony; thus, attention must be paid to intra-left ventricular dyssynchrony and cardiac dysfunction. Whether intra-left ventricular systolic dyssynchrony can resolve within 1 month may be a new early predictor of patient prognosis.

Comparison of ventricular synchrony in children with left bundle branch area pacing and right ventricular septal pacing.

OBJECTIVE: This study aimed to determine the ideal pacing site in children by comparing the postoperative ventricular synchrony in children with left bundle branch area pacing and those with right ventricular septal pacing. METHODS: This retrospective study included children with complete atrioventricular block who underwent permanent pacemaker implantation from March 2019 to August 2021. Patients were grouped according to their ventricular pacing site, the left bundle branch area pacing group and the right ventricular septal pacing group. Two-dimensional speckle tracking echocardiography was used to evaluate the ventricular synchrony. RESULTS: Forty-eight children (median age, 2.7 years; interquartile range, 1.7-4.6 years) were included. The paced QRS duration in the left bundle branch area pacing group was significantly narrower than that in the right ventricular septal pacing group (100.2 ± 9.3 versus 115.4 ± 15.1 ms, p = 0.001). The median follow-up duration was 1.5 years (interquartile range, 1-2 years). At the last follow-up, the average capture threshold of the ventricular electrode in the left bundle branch area pacing group was lower than that in the right ventricular septal pacing group (0.79 ± 0.18 versus 1.20 ± 0.56 V, p = 0.008). The left ventricular intraventricular synchrony parameters in the left bundle branch area pacing group were better than those in the right ventricular septal pacing group (e.g. standard deviation of the time to peak longitudinal strain, 37.4 ± 4.3 versus 46.6 ± 8.2 ms, p = 0.000). The average interventricular mechanical delay time in the left bundle branch area pacing group was significantly shorter than that in the right ventricular septal pacing group (36.4 ± 14.2 versus 52.5 ± 22.7 ms, p = 0.016). CONCLUSION: Compared with right ventricular septal pacing, left bundle branch area pacing in children produces a narrower QRS duration and better pacing and ventricular synchrony parameters postoperatively.

MIB1-mediated degradation of WRN promotes cellular senescence in response to camptothecin treatment.

Werner syndrome protein (WRN) plays critical roles in DNA replication, recombination, and repair, as well as transcription and cellular senescence. Ubiquitination and degradation of WRN have been reported, however, the E3 ubiquitin ligase of WRN is little known. Here, we identify mindbomb E3 ubiquitin protein ligase 1 (MIB1) as a novel E3 ubiquitin ligase for WRN protein. MIB1 physically interacts with WRN in vitro and in vivo and induces ubiquitination and degradation of WRN in the ubiquitin-proteasome pathway. Camptothecin (CPT) enhances the interaction between MIB1 and WRN, and promotes WRN degradation in a MIB1-dependent manner. In addition, CPT-induced cellular senescence is facilitated by the expression of MIB1 and attenuated by WRN expression. Our results show that MIB1-mediated degradation of WRN promotes cellular senescence and reveal a novel model executed by MIB1 and WRN to regulate cellular senescence.

Association between severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery after ablation in children.

OBJECTIVE: To investigate the association between the severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery time after catheter ablation and identify predictors of cardiac function recovery after ablation. METHODS AND RESULTS: A total of 49 children underwent successful ablation (median 2.92 years). This study included 23 patients with mild cardiac dysfunction (left ventricular ejection fraction [LVEF]: 45% ≤ LVEF ≤ 55%), 15 with moderate (30% ≤ LVEF < 45%), and 11 with severe (LVEF <30%). The time for mean LVEF reaching 55% was 0.75, 3, and more than 12 months, respectively. The mean LVEF of children with severe cardiac dysfunction aged ≤6 years normalized within 12 months of follow-up (63.00% ± 1.41%). Mean LVEF of those aged more than 6 years did not normalize at 12 months of follow-up (38.67% ± 10.97%). LVEF recovery time was significantly different between these two age groups (median 11 months vs >12 months, χ2 = 4.55; P = .04). Cox regression analysis showed that preablation smaller left ventricular diastolic diameter (LVDd) Z score and higher LVEF were predictors of cardiac dysfunction recovery time (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.82-0.99, P = .04; HR = 1.09, 95% CI = 1.03-1.15, P = .01). CONCLUSION: Patients with higher LVDd Z scores and lower LVEF tend to have slower improvement in cardiac function after ablation. Patients with LVEF less than 30% and aged more than 6 years need more than 12 months to fully recover, and some might not even completely recover. Early catheter ablation is suggested once ventricular pre-excitation-led cardiac dysfunction is suspected.

G9a coordinates with the RPA complex to promote DNA damage repair and cell survival.

Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.

Electrophysiological Characteristics and Outcomes of Radiofrequency Catheter Ablation of Atrial Flutter in Children with or Without Congenital Heart Disease.

There are scarce studies on radiofrequency catheter ablation (RFCA) of atrial flutter (AFL) in the pediatric population. This study therefore aimed to investigate the clinical features and RFCA of AFL in children with or without congenital heart disease. Data from 72 consecutive children (44 males; mean age, 6.1 ± 3.8 [0.9-15.0] years; and mean weight, 23.6 ± 13.9 [8.1-72.0] kg) undergoing RFCA for AFL from 2009 to 2019 were retrospectively reviewed. Thirty-three patients had normal cardiac structure and 39 had congenital heart disease (CHD) of whom 29 had undergone surgical repair and developed AFL at a mean of 3.1 ± 2.5 years later. Fifty-nine patients (84%) presented with persistent AFL. Five patients (7%) had cardiac dysfunction with LVEF of 30-48%, which normalized after ablation. Overall, acute success rate of ablation was 99% and recurrence rate was 18% at 0.5-10 years of follow-up. No procedure-related complications were identified. All 33 patients with normal cardiac structure had cavotricuspid isthmus (CTI)-dependent AFL. Among patients who had undergone corrective surgery for CHD, 15 (52%) had CTI-dependent AFL, 4 (14%) had surgical incisional scar reentrant AFL and the remaining 10 (34%) had both CTI-dependent and scar reentrant AFL. Success rate (100% vs. 97%, P = 1.0000) and recurrence rate (21% vs. 16%, P = 0.7008) were similar between patients with and without CHD. Overall, sick sinus syndrome (SSS) was found in 42% (30/72) of patients with AFL, with an incidence of 39% (13/33) among patients with normal cardiac structure and 59% (17/29) among those who underwent surgery for congenital defects. Permanent pacemakers (PM) were implanted in 53% (16/30) of patients with SSS after ablation. RFCA therefore appeared efficacious and safe for treatment of pediatric AFL. The mechanisms underlying AFL after corrective surgery for CHD are complex, including CTI-dependent macro-reentrant, scar reentrant, or a combination of both. SSS is not rare among pediatric AFL cases, with approximately half of patients needing PM implantation.

Morphology Tailoring of ZnWO4 Crystallites/Architectures and Photoluminescence of the Doped RE3+ Ions (RE = Sm, Eu, Tb, and Dy).

Tartrate (Tar2-) was originally employed in this work as a chelating/structure-directing agent for hydrothermal crystallization of ZnWO4, where the decisive roles of Tar2-/Zn2+/WO42- molar ratio, solution pH (7-10), and the use of ethylene glycol (EG) cosolvent in phase/morphology evolution were deciphered in detail. It was unambiguously manifested that Tar2- may remarkably retard the intrinsically preferred [001] growth of ZnWO4, transform 1D nanorods to 0D nanoparticles and then to 2D platelets, and meanwhile induce face-to-face alignment of the platelets to form spheroidal, ellipsoidal and snowflakelike 3D architectures, where the 2D crystallites were revealed to develop via oriented attachment (colattice) of non-(00l) facets. A lower solution pH and excessive WO42- were clearly shown to enhance and offset the effect of Tar2-, which led to ellipsoidal assemblies of substantially larger 2D crystallites and suppressed 2D growth/3D assembly of ZnWO4 crystallites, respectively. With the spheroidal architectures for example, doping ZnWO4 with RE3+ yielded (Zn0.98RE0.02)WO4 phosphors (RE = Sm, Eu, Tb, and Dy, respectively) that show luminescence overlapped from the typical linelike and broad-band (∼350-700 nm) emissions of RE3+ and WO6, respectively. The luminescence color of the sample was found to drift away from the blue corner of the CIE chromaticity diagram with RE3+ doping and to be dependent on the type of RE3+.

SET7/9 regulates cancer cell proliferation by influencing ß-catenin stability.

ß-Catenin, which is a key mediator of the wingless-integration site (Wnt)/ß-catenin signaling pathway, plays an important role in cell proliferation, cell fate determination, and tumorigenesis, by regulating the expression of a wide range of target genes. Although a variety of posttranslational modifications are involved in ß-catenin activity, the role of lysine methylation in ß-catenin activity is largely unknown. In this study, su(var)3-9, enhancer-of-zeste, trithorax (SET) domain-containing protein 7 (SET7/9), a lysine methyltransferase, interacted with and methylated ß-catenin, as demonstrated both in vitro and in vivo. The interaction and methylation were significantly enhanced in response to H2O2 stimulation. A mutagenesis assay and mass spectrometric analyses revealed that ß-catenin was monomethylated by SET7/9 at lysine residue 180. Methylated ß-catenin was easily recognized by phosphokinase glycogen synthase kinase (GSK)-3ß for degradation. Consistent with this finding, the mutated ß-catenin (K180R) that cannot be methylated exhibited a longer half-life than did the methylated ß-catenin. The consequent depletion of SET7/9 by shRNA or the mutation of the ß-catenin (K180R) significantly enhanced the expression of Wnt/ß-catenin target genes such as c-myc and cyclin D1 and promoted the growth of cancer cells. Together, these results provide a novel mechanism by which Wnt/ß-catenin signaling is regulated in response to oxidative stress.

Effectiveness of Radiofrequency Catheter Ablation of Outflow Tract Ventricular Arrhythmias in Children and Adolescents.

Outflow tract ventricular arrhythmias (OTVAs) are common in children; however, experience is limited on their radiofrequency catheter ablation (RFCA). The purpose of this study was to assess the outcomes of mapping and ablation of pediatric OTVAs and to evaluate the role of ECG algorithms in distinguishing the origin of OTVAs. We compared retrospectively collected single-center data on 92 consecutive pediatric patients (58 male; age, 8.2 ± 2.9 [range 3.6-18] years) who underwent RFCA for OTVAs from 2009 to 2015. Two independent and blinded observers analyzed ECG data. Of these children, 69 (75 %) were of RVOT origin. RFCA was given up in 1 case, and the acute success rate was 92.3 % (84/91), the 1-year follow-up recurrence rate was 8.3 % (7/84) and the complications of the procedure were 2.2 % (2/92). And 3D versus 2D mapping-guided RFCA was associated with significantly (p < 0.05) higher acute success rate (96.1 % [49/51] vs. 87.5 % [35/40]), and lower X-ray exposure (742.5 ± 323.1 vs. 1432.3 ± 605.5 mGy cm2) and 1-year recurrence rate (4.1 % [2/49] vs. 14.3 % [5/35]). The positive predictive value of four types of ECG algorithms used in adults for LVOT origin was only 47.7-65.4 %. In these cases, four identified as RVOT origin and two identified as LVOT origin by ECG underwent successful ablation on the other side of outflow tract finally. And these six children who underwent successful RFCA in both sides of outflow tract had no follow-up recurrence. OTVAs in children originate mostly from RVOT. RFCA can be used for ablation of pediatric OTVAs effectively and safely. In some cases, successful RFCA should be ablated in both sides of outflow tract. ECG-based prediction of OTVA origin as used in adults is limited in children.

[The Roles of Sirtuins in DNA Damage and Repair].

Sirtuins, class III HDAC, has originally been defined as a family of nicotinamide adenine dinucleotide-dependent enzymes. There are seven mammalian sirtuins (SIRTI07), which mainly deaceylate lysine residue on various proteins as a deacetylase. Sirtuins regulate a diverse array of biological processes, including DNA damage and repair, gene transcription regulation, apoptosis, metabolism and aging. In this research perspective we review the role and molecular mechanism of Sirtuin in DNA damage and repair.

[The role of epigenetic modification in glucose and lipid metabolism].

Epigenetics refers to heritable changes in gene expression without alteration of the DNA sequence. Epigenetic changes play an important role in a variety of biological processes including glucose and lipid metabolism. Glucose and lipid metabolism is closely related each other in vivo and abnormal lipid and glucose metabolism is able to cause multiple metabolic related diseases. This review focuses on recent advances of DNA methylation, histone modification, and non-coding RNA on regulating glucose and lipid metabolism.

Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

Exploratory and confirmatory factor analysis of the sensitivity to punishment and sensitivity to reward questionnaire-revised and its psychometric evaluation among Chinese person with substance use disorder.

The Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) is a self-report tool widely used to assess individuals' level of reinforcement sensitivity. Drug addiction is strongly associated with reinforcement sensitivity, but there is a lack of measurement tools to assess reinforcement sensitivity in drug users, necessitating the revision and application of the SPSRQ among drug users. This study recruited 819 drug users (mean age = 34.74; 56.41% female) from five compulsory rehabilitation centers in Hunan Province, China. The applicability of the SPSRQ among person with substance use disorder was assessed by conducting reliability analyses and validity analyses, with retesting performed by 127 individuals after 6 weeks. Exploratory factor analysis for the SPSRQ showed a stable two-factor structure in person with substance use disorder. Confirmatory factor analysis indicated acceptable goodness of fit indexes for the two-factor structure. The SPSRQ also demonstrated good reliability and convergent and discriminant validity evidence. The two-factor structure of the SPSRQ also demonstrated measurement invariance across gender. Further comparative analysis found that the degree of reward sensitivity was higher for males than for females. Generally, the SPSRQ has shown evidence of good reliability and validity in Chinese drug-dependent populations, and it is suitable for research and application with Chinese person with substance use disorder. These findings about the personality traits of people with substance use disorder provide a solid basis for further research.

[Study on relationship between alfalfa canopy spectral reflectance and leaf water content].

In the present study, alfalfa canopy reflectance was researched at alfalfa squaring period under different irrigation amount at the hutubi county grassland ecological station. Determining the spectral diagnostic model of alfalfa leaf moisture content was determined by spectrometry. The results showed that (1) The spectral reflectance of alfalfa canopy gradually decreases with the increase in the leaf water content in the near infrared. (2) The spectral inversion model of alfalfa leaf moisture content established by normalized reflectance spectra is superior to the original reflectance spectra, and the prediction model established in the 1,344-1,660 nm band has the lowest average relative error (7.8%). (3) In this study, the spectral diagnostic model of the leaf moisture content is: Y=0.962 - 7.560X1451 + 5.295X1473. The spectral prediction model of the alfalfa leaf moisture content can provide a basis for decision making for scientific irrigation of alfalfa.

SLC25A51 promotes tumor growth through sustaining mitochondria acetylation homeostasis and proline biogenesis.

Solute carrier family 25 member 51 (SLC25A51) was recently identified as the mammalian mitochondrial NAD+ transporter essential for mitochondria functions. However, the role of SLC25A51 in human disease, such as cancer, remains undefined. Here, we report that SLC25A51 is upregulated in multiple cancers, which promotes cancer cells proliferation. Loss of SLC25A51 elevates the mitochondrial proteins acetylation levels due to SIRT3 dysfunctions, leading to the impairment of P5CS enzymatic activity, which is the key enzyme in proline biogenesis, and the reduction in proline contents. Notably, we find fludarabine phosphate, an FDA-approved drug, is able to bind with and inhibit SLC25A51 functions, causing mitochondrial NAD+ decrease and proteins hyperacetylation, which could further synergize with aspirin to reinforce the anti-tumor efficacy. Our study reveals that SLC25A51 is an attractive anti-cancer target, and provides a novel drug combination of fludarabine phosphate with aspirin as a potential cancer therapy strategy.

Tumor microenvironment-activated Nb2C quantum dots/lactate oxidase nanocatalyst mediates lactate consumption and macrophage repolarization for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), which takes advantages of CDT agents to selectively induce tumor cells apoptosis via Fenton or Fenton-like reactions, is considered to have great potential for tumor-specific treatment. However, the therapeutic outcome of CDT still faces the challenges of the lack of efficient CDT agents and insufficient supply of endogenous H2O2. Herein, to explore highly efficient CDT agents as well as increase the H2O2 content at tumor sites to enhance the efficiency of CDT, a red blood cell (RBC) membrane encapsulated Nb2C quantum dots/lactate oxidase (LOD) nanocatalyst (Nb2C QDs/LOD@RBC) was proposed. Nb2C quantum dots are quite prospective as efficient CDT agents in CDT application due to the intrinsic merits such as abundant active catalytic sites, satisfactory hydrophilicity, and good biocompatibility. The encapsulation of Nb2C QDs and LOD into RBC membrane was to prolong the in vivo circulation time of the nanocatalyst and increase its tumor sites accumulation. The accumulated Nb2C QDs/LOD@RBC nanocatalyst could efficiently convert the endogenous H2O2 into ·OH, while the overexpressed lactate could be catalyzed into H2O2 by LOD to replenish the depletion of H2O2. The cascaded reaction between Nb2C quantum dots and LOD eventually enhanced the CDT effect of Nb2C QDs/LOD@RBC nanocatalyst for tumors growth inhibition. Moreover, the consumption of lactate at tumor sites induced by Nb2C QDs/LOD@RBC nanocatalyst leads to the increased infiltration of antitumoral M1 tumor-associated macrophages, which alleviated the immunosuppression of the tumor microenvironment and further maximized the therapeutic outcome of CDT. Taken together, the Nb2C QDs/LOD@RBC nanocatalyst provides a promising paradigm for tumor inhibition via catalytic cascaded reaction between Nb2C quantum dots and LOD.