RMTLysPTM: recognizing multiple types of lysine PTM sites by deep analysis on sequences.

Post-translational modification (PTM) occurs after a protein is translated from ribonucleic acid. It is an important living creature life phenomenon because it is implicated in almost all cellular processes. Identification of PTM sites from a given protein sequence is a hot topic in bioinformatics. Lots of computational methods have been proposed, and they provide good performance. However, most previous methods can only tackle one PTM type. Few methods consider multiple PTM types. In this study, a multi-label classification model, named RMTLysPTM, was developed to recognize four types of lysine (K) PTM sites, including acetylation, crotonylation, methylation and succinylation. The surrounding sites of a lysine site were selected to constitute a peptide segment, representing the lysine at the center. Deep analysis was conducted to count the distribution of 2-residues with fixed location across the four types of lysine PTM sites. By aggregating the distribution information of 2-residues in one peptide segment, the peptide segment was encoded by informative features. Furthermore, a prediction engine that can precisely capture the traits of the above representations was designed to recognize the types of lysine PTM sites. The cross-validation results on two datasets (Qiu and CPLM training datasets) suggested that the model had extremely high performance and RMTLysPTM had strong generalization ability by testing it on protein Q16778 and CPLM testing datasets. The model was found to be generally superior to all previous models and those using popular methods and features. A web server was set up for RMTLysPTM, and it can be accessed at http://119.3.127.138/.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Na2.5Cr0.5Zr0.5Cl6: A New Halide-Based Fast Sodium-Ion Conductor.

All-solid-state batteries employing solid electrolytes (SEs) have received widespread attention due to their high safety. Recently, lithium halides are intensively investigated as promising SEs while their sodium counterparts are less studied. Herein, a new sodium-ion conductor with a chemical formula of Na2.5Cr0.5Zr0.5Cl6 is reported, which exhibits high room temperature ionic conductivity of 0.1 mS cm-1 with low migration energy barrier of ≈0.41 eV. Na2.5Cr0.5Zr0.5Cl6 has a Fm-3m structure with 41.67 mol.% of cationic vacancies owing to the occupation of Cr (8.33 mol.%) and Zr (8.33 mol.%) ions at Na sites. Supercell calculations show that the lowest columbic energy configuration has Cr/Zr/V (where V is the vacancy) clusters in the structure. Nonetheless, the clusters have mixed effects on the sodium ion conduction pathway, based on the Bond Valence Energy Landscape calculation. A global 3D Na-ion transport percolation network can be revealed in the lowest energy supercell. Effective pathways are connected through the NaCl6 and VCl6 nodes. Besides, Raman spectroscopy and 23Na solid-state nuclear magnetic resonance spectroscopy further prove the tunable structure of the SEs with different Cr to Zr ratios. The optimization between the concentration of Na+ and vacancies is crucial to create an improved network of Na+ diffusion channels.

28.02 W LD side-pumped CW laser operated at 2.8†µm in YSGG/Er:YSGG/YSGG crystal.

We demonstrated a 978 nm laser diode (LD) side-pumped YSGG/Er:YSGG/YSGG composite crystal with a size of Ф 3 mm × 65 mm and continuous-wave (CW) mode. By optimizing resonator length and output mirror transmittance, a maximum output power of 28.02 W is generated, corresponding to slope efficiency of 17.55% and optical-optical efficiency of 12.29%, respectively. The thermal focal lengths are obtained by resonator stability condition. The laser wavelength is centered near 2.8 µm. Moreover, the beam quality factors M x2/M y2 are fitted to be 8.14 and 7.35, respectively. The above results indicate that a high-performance 2.8 µm CW laser can be achieved by LD side-pumped YSGG/Er:YSGG/YSGG composite crystal with excellent heat dissipation ability, which promotes effectively the development and applications of the mid-infrared solid-state lasers.

Effect of different anti-cardiovascular disease treatments on the severity of obstructive sleep apnea.

Obstructive sleep apnea (OSA) and cardiovascular co-morbidities have a mutually reinforcing effect, but existing studies have focussed only on the improvement of the associated co-morbidities by treatment for OSA. To provide fresh guidelines for the treatment of OSA from a co-morbidity standpoint, we conducted a systematic search of Web of Science, PubMed, EMBASE, and the Cochrane Library for articles published from inception up to 2 May 2023. Fourteen original studies of patients with OSA with cardiovascular co-morbidities and who received related treatment were included in the analysis. We found that diuretic treatment can reduce the apnea-hypopnea index in patients with OSA and hypertension (-19.41/h, p = 1.0 × 10-5 ), aldosterone-angiotensin inhibitors also have a 9.19/h reduction (p = 0.003), while the effect of renal sympathetic denervation is insignificant (-2.32/h, p = 0.19). The short-term treatment (<4 weeks) did not show an improvement (-2.72/h, p = 0.16), while long-term treatment (>4 weeks) produced surprising outcomes (-12.78/h, p = 0.002). Patients with milder disease (baseline AHI < 35/h) had insignificant improvements (-1.05/h, p = 0.46), whereas those with more severe disease (baseline AHI > 35/h) could achieve satisfactory outcomes (-14.74/h, p < 0.00001). In addition, it also showed some improvement in the oxygen desaturation index and blood oxygen. Our results support the additional benefit of antihypertensive treatment for OSA symptoms, and the efficacy can be affected by different therapy, treatment duration, and severity levels. It could be useful in developing clinical therapy, educating patients, and exploring interaction mechanisms. The proposal was registered with PROSPERO (CRD42022351206).

Optimized MLPA workflow for spinal muscular atrophy diagnosis: identification of a novel variant, NC_000005.10:g.(70919941_70927324)del in isolated exon 1 of SMN1 gene through long-range PCR.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal recessive hereditary neuromuscular disease caused by survival motor neuron 1 (SMN1) gene deletion or mutation. Homozygous deletions of exon 7 in SMN1 result in 95% of SMA cases, while the remaining 5% are caused by other pathogenic variants of SMN1. METHODS: We analyzed two SMA-suspected cases that were collected, with no SMN1 gene deletion and point mutation in whole-exome sequencing. Exon 1 deletion of the SMN gene was detected using Multiplex ligation-dependent probe amplification (MLPA) P021. We used long-range polymerase chain reaction (PCR) to isolate the SMN1 template, optimized-MLPA P021 for copy number variation (CNV) analysis within SMN1 only, and validated the findings via third-generation sequencing. RESULTS: Two unrelated families shared a genotype with one copy of exon 7 and a novel variant, g.70919941_70927324del, in isolated exon 1 of the SMN1 gene. Case F1-II.1 demonstrated no exon 1 but retained other exons, whereas F2-II.1 had an exon 1 deletion in a single SMN1 gene. The read coverage in the third-generation sequencing results of both F1-II.1 and F2-II.1 revealed a deletion of approximately 7.3 kb in the 5' region of SMN1. The first nucleotide in the sequence data aligned to the 7385 bp of NG_008691.1. CONCLUSION: Remarkably, two proband families demonstrated identical SMN1 exon 1 breakpoint sites, hinting at a potential novel mutation hotspot in Chinese SMA, expanding the variation spectrum of the SMN1 gene and corroborating the specificity of isolated exon 1 deletion in SMA pathogenesis. The optimized-MLPA P021 determined a novel variant (g.70919941_70927324del) in isolated exon 1 of the SMN1 gene based on long-range PCR, enabling efficient and affordable detection of SMN gene variations in patients with SMA, providing new insight into SMA diagnosis to SMN1 deficiency and an optimized workflow for single exon CNV testing of the SMN gene.

Analytical validation of the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis assay to diagnose spinal muscular atrophy.

OBJECTIVES: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletion and compound heterozygous mutations in survival motor neuron 1 (SMN1), with severity tied to the copy number of survival motor neuron 2 (SMN2). This study aimed to develop a rapid and comprehensive method for the diagnosis of SMA. METHODS: A total of 292 children with clinically suspected SMA and 394 family members were detected by the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis (ARMS-PCR-CE) method, which targeted 19 reported mutations, and the results were compared with those in multiplex ligation-dependent probe amplification (MLPA). Individuals with identified point mutations were further confirmed by SMN1 long-range PCR and Sanger sequencing. RESULTS: A total of 202 children with SMA, 272 carriers, and 212 normal individuals were identified in this study. No difference was found in the R-value distribution of exons 7 and 8 in SMN1 and SMN2 among these cohorts, with coefficients of variation consistently below 0.08. To detect exon 7 and 8 copy numbers in SMN1 and SMN2, the ARMS-PCR-CE results were concordant with those of MLPA. Approximately 4.95 % (10/202) of the study patients had compound heterozygous mutations. CONCLUSIONS: The ARMS-PCR-CE assay is a comprehensive, rapid, and accurate diagnostic method for SMA that simultaneously detects copy numbers of exons 7 and 8 in SMN1/SMN2, as well as 19 point mutations in SMN1 and 2 enhancers in SMN2. This approach can effectively reduce the time frame for diagnosis, facilitating early intervention and preventing birth defects.

Polar Molecules Regulating the Regio- and Stereoselectivity of Polymerization of Conjugated Dienes Catalyzed by CGC-Type Rare-Earth Metal Catalysts.

Herein, a concise, effective, and scalable strategy is reported that the introduction of polar molecules (PMs) (e.g., anisole (PhOMe), phenetole (PhOEt), 2-methoxynaphthalene (NaphOMe), thioanisole (PhSMe), and N,N-dimethylaniline (PhNMe2)) as continuously coordinated neutral ligand of cationic active species in situ generated from the constrain-geometry-configuration-type rare-earth metal complexes A-F/AliBu3/[Ph3C][B(C6F5)4] ternary systems can easily switch the regio- and stereoselectivity of the polymerization of conjugated dienes (CDs, including 2-subsituted CDs such as isoprene (IP) and myrcene (MY), 1,2-disubstituted CD ocimene (OC), and 1-substituted polar CD 1-(para-methoxyphenyl)-1,3-butadiene (p-MOPB)) from poor selectivities to high selectivities (for IP and MY: 3,4-selectivity up to 99%; for OC: trans-1,2-selectivity up to 93% (mm up to 90%); for p-MOPB: 3,4-syndioselectivity (3,4- up to 99%, rrrr up to 96%)). DFT calculations explain the continuous coordination roles of PMs on the regulation of the regio- and stereoselectivity of the polymerization of CDs. In comparison with the traditional strategies, this strategy by adding some common PMs is easier and more convenient, decreasing the synthetic cost and complex operation of new metal catalyst and cocatalyst. Such regio- and stereoselective regulation method by using PMs is not reported for the coordination polymerization of olefins catalyzed by rare-earth metal and early transition metal complexes.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Gain of C-Ala enables AlaRS to target the L-shaped tRNAAla.

Unlike many other aminoacyl-tRNA synthetases, alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout biology. While Caenorhabditis elegans cytoplasmic AlaRS (CeAlaRSc) retains the prototype structure, its mitochondrial counterpart (CeAlaRSm) contains only a residual C-terminal domain (C-Ala). We demonstrated herein that the C-Ala domain from CeAlaRSc robustly binds both tRNA and DNA. It bound different tRNAs but preferred tRNAAla. Deletion of this domain from CeAlaRSc sharply reduced its aminoacylation activity, while fusion of this domain to CeAlaRSm selectively and distinctly enhanced its aminoacylation activity toward the elbow-containing (or L-shaped) tRNAAla. Phylogenetic analysis showed that CeAlaRSm once possessed the C-Ala domain but later lost most of it during evolution, perhaps in response to the deletion of the T-arm (part of the elbow) from its cognate tRNA. This study underscores the evolutionary gain of C-Ala for docking AlaRS to the L-shaped tRNAAla.

Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

Evaluation of the Feasibility of In Vitro Metabolic Interruption of Trimethylamine with Resveratrol Butyrate Esters and Its Purified Monomers.

Resveratrol (RSV), obtained from dietary sources, has been shown to reduce trimethylamine oxide (TMAO) levels in humans, and much research indicates that TMAO is recognized as a risk factor for cardiovascular disease. Therefore, this study investigated the effects of RSV and RSV-butyrate esters (RBE) on the proliferation of co-cultured bacteria and HepG2 cell lines, respectively, and also investigated the changes in trimethylamine (TMA) and TMOA content in the medium and flavin-containing monooxygenase-3 (FMO3) gene expression. This study revealed that 50 µg/mL of RBE could increase the population percentage of Bifidobacterium longum at a rate of 53%, while the rate was 48% for Clostridium asparagiforme. In contrast, co-cultivation of the two bacterial strains effectively reduced TMA levels from 561 ppm to 449 ppm. In addition, regarding TMA-induced HepG2 cell lines, treatment with 50 µM each of RBE, 3,4'-di-O-butanoylresveratrol (ED2), and 3-O-butanoylresveratrol (ED4) significantly reduced FMO3 gene expression from 2.13 to 0.40-1.40, which would also contribute to the reduction of TMAO content. This study demonstrated the potential of RBE, ED2, and ED4 for regulating TMA metabolism in microbial co-cultures and cell line cultures, which also suggests that the resveratrol derivative might be a daily dietary supplement that will be beneficial for health promotion in the future.

An evaluation of intervention appropriateness from the perspective of parents: A peer-mediated, play-based intervention for children with ADHD.

INTRODUCTION: A peer-mediated, play-based intervention has been developed to address social participation challenges experienced by children with ADHD. To facilitate implementation into clinical practice, interventions should be evaluated for appropriateness to the end-user, as well as effectiveness. Previous research demonstrated the approach is effective for improving children's social play skills. This study aimed to evaluate the appropriateness of the intervention for children with ADHD and their families. METHODS: Parents of children with ADHD who participated in the play-based intervention were interviewed 1 month after completion. Parents were asked about their perspective of parent and children's experiences of the intervention, the perceived benefits for children and parents, the logistics of participating, and recommended adaptations to the intervention. Interviews were analysed thematically, and themes were mapped to the elements of the adopted definition of appropriateness to understand whether parents supported the appropriateness of the intervention for their families. CONSUMER AND COMMUNITY INVOLVEMENT: Consumers were not directly involved in the decisions made about this study. FINDINGS: One core theme, 'collaborative efforts', emerged from the data. Major themes comprising the core theme were 'on the same page', 'therapeutic relationship', and 'getting the job done'. Three sub-themes of 'engagement and motivation', 'the effort was worth it for the reward', and 'Rome wasn't built in a day' were nested within the major themes. CONCLUSION: Parents largely supported the appropriateness of the intervention, indicating it addressed an important goal for their child, participation was a positive experience, and they perceived the intervention to be beneficial. Future adaptions of the intervention are needed to increase its ecological validity and to generalise the strategies to other social environments and playmates, such as peers at school. PLAIN LANGUAGE SUMMARY: This study looked at an intervention that uses play with peers to help children with ADHD develop their play skills. The researchers wanted to know if parents thought the intervention was a good fit for their families and if it helped their children. Parents gave an interview a month after the intervention ended. They were asked about their thoughts on the intervention, how it helped their children and themselves, how easy it was to take part, and what changes could be made to make the intervention better. After analysing parents' answers, the researchers found parents mostly agreed that the intervention was a good fit. They said it helped their children to play with their peers, and they had a good time doing it. Parents thought the intervention was helpful, they liked that it was a joint effort between them and the occupational therapist, and they felt it was worth the effort. However, they also suggested some changes. They wanted the intervention to fit into other real-life social situations, such as school, so their children could use the skills they learned in other places. Overall, parents thought the intervention was helpful and suitable for their children and themselves, but some changes might make it more helpful.

HDAC3 Controls Liver Homeostasis More by Facilitating Deoxyribonucleic Acid Damage Repair than by Regulating Transcription in Hepatocytes.

By controlling DNA damage repair and regulating gene transcription, the critical epigenetic regulator histone deacetylase 3 (HDAC3) plays pivotal roles in liver cancer and liver regeneration; however, the role of HDAC3 in liver homeostasis has not been fully elucidated. In this study, we found that HDAC3-deficient livers developed a defective morphology and metabolism with an increasing degree of DNA damage in the hepatocytes along the portal-central axis of the lobule. Most strikingly, in the Alb-CreERT:Hdac3-/- mice, it was demonstrated that HDAC3 ablation did not impair liver homeostasis in terms of histologic characteristics, function, proliferation, or gene profiles prior to the profound accumulation of DNA damage. Next, we identified that the hepatocytes in the portal area, which carried less DNA damage than those in the central area, repopulated the hepatic lobule by active regeneration and movement toward the center. As a result, the liver became more viable after each surgery. Furthermore, in vivo tracing of keratin-19-expressing hepatic progenitor cells, which lacked HDAC3, showed that the hepatic progenitor cells gave rise to newly generated periportal hepatocytes. In hepatocellular carcinoma, HDAC3 deficiency impaired DNA damage response and enhanced radiotherapy sensitivity in vitro and in vivo. Taken together, we demonstrated that HDAC3 deficiency interferes with liver homeostasis, which is more dependent on the accumulation of DNA damage in hepatocytes than on transcriptional dysregulation. Our findings support the hypothesis that selective HDAC3 inhibition has the potential to augment the effect of chemoradiotherapy aimed at inducing DNA damage in cancer therapy.

Increased Small Ubiquitin-like Modifier-Activating Enzyme SAE1 Promotes Hepatocellular Carcinoma by Enhancing mTOR SUMOylation.

SUMOylation, one of the most important posttranslational modifications of proteins, plays an essential role in various biological processes; however, enzymes that control SUMOylation in hepatocellular carcinoma (HCC) are still unclear. Comprehensive exploration of the expression and clinical significance of SUMO enzymes in HCC would be of great value. Here, we obtained the gene expression profile of each small ubiquitin-like modifier (SUMO) protein and the corresponding clinical information from The Cancer Genome Atlas. We found that all SUMO enzymes were significantly increased in HCC tissues compared with that in adjacent nontumorous tissues. We identified a 6-gene prognostic signature, including SAE1, PIAS2, PIAS3, SENP3, SENP5, and UBC9, that could effectively predict the overall survival in patients with HCC. Specifically, SAE1 was the most valuable prognostic indicator. In 282 clinical samples, we found that SAE1 was closely related to the clinicopathologic parameters and prognosis of patients with HCC. In vitro and in vivo studies showed that SAE1 knockdown inhibits the proliferation, migration, and invasion of HCC cells. Mechanistically, we confirmed that SAE1 plays a role in driving HCC progression, which is largely dependent on the SUMOylation of mTOR signaling. In conclusion, our study revealed that the expression of SUMO enzymes, especially SAE1, is highly associated with HCC development and acts as a promising prognostic predictor.

5.32 W ultraviolet laser generation at 266†nm using sum-frequency method with CsB3O5 crystal.

Ultraviolet (UV) beam generation at 266 nm using the sum-frequency (SFG) method with CsB3O5 (CBO) crystals was first suggested in 1997 [Opt. Lett.22, 1840 (1997).10.1364/OL.22.001840]; however, there has been no further research in the past 25 years. Herein, by sum-frequency mixing in CBO crystals, we obtained a high conversion efficiency picosecond (ps) and a high-power nanosecond (ns) 266 nm UV beam output. First, a ps laser device with simultaneously radiated wavelengths of 1064 and 355 nm and repetition frequency of 10 Hz was used as the fundamental laser source, and the conversion efficiency from 1064 + 355 nm to 266 nm reached 20.35%. We then used a 1064 nm ns laser with a high output power and repetition frequency of 10 kHz as the pump source. We accurately modified the optimal phase matching direction of the CBO crystal, and the achieved output power at 266 nm reached 5.32 W.

Structure, spectroscopy and laser performance of an Er:YGGAG crystal.

In this work, we report on investigations of structure, spectroscopic properties and laser performances of, what we believe to be, a novel Er:YGGAG laser crystal. High crystalline quality is proved by an FWHW of XRC of 0.019°. Thermal conductivity of a 30 at.% Er:YGGAG crystal is determined as 4.98 W/(m·K). The refractive index is measured in the range of 400 to 1000 nm and fitting with Sellmeier equation is done. A broad fluorescence emission band is located at 2786∼2819 nm, suggesting that this crystal is favorable to realize tunable and ultrafast laser. Under the pump at 969 nm with a fiber-coupled diode laser, at 400 Hz repetition rate and 600 µs pulse duration, the 30 at.% Er:YGGAG delivered maximum average power of 506 mW with overall optical-to-optical efficiency of 12.4% and slope efficiency of 16.9%. The laser beam quality was characterized by M2 factors of 1.53 and 1.39 in horizontal and vertical directions, respectively.

Thermal, spectroscopy and optimized ∼3†µm CW laser properties for Ho,Pr:YAP crystal.

We demonstrate the thermal, spectroscopy and laser properties of Ho,Pr doped YAP crystal grown successfully by Cz method. The thermal expansion coefficient, thermal conductivity, absorption and emission spectra of Ho,Pr:YAP crystal are investigated in detail. Additionally, the level lifetimes suggest that Pr3+ is a suitable deactivating ion for Ho:YAP crystal. Particularly, the actual laser performance is optimized by doping active ion Ho with high concentrations and introducing deactivated Pr3+, resulting in decreased laser threshold, increased laser output power and slope efficiency. A 3.01 µm laser with output power of 502 mW, slope efficiency of 6.3% and beam quality factors of 1.42/1.43 is achieved in the Ho,Pr:YAP crystal, as far as we know this is the highest ∼3 µm CW laser power realized in Ho3+ doped oxide crystals.

Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages. METHODS: Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6-/-) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells. RESULTS: We observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC. CONCLUSION: In summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.

Improvement on Magnetocaloric Effect through Structural Evolution in Gadolinium Borate Halides Ba2Gd(BO3)2X (X = F, Cl).

A new Gd3+-containing borate Ba2Gd(BO3)2F has been successfully grown via the high-temperature solution method using BaF2-NaF-B2O3 flux. Ba2Gd(BO3)2F crystallizing in the orthorhombic space group Pnma is with lattice parameters a = 7.571(4) Å, b = 10.424(5) Å, c = 8.581(4) Å, α = ß = γ = 90°, and Z = 2. Its three-dimensional framework was constructed from interesting pinwheel-like [Gd(BO3)F]∞ layers bridged by sharing [BO3]3-, which is different from the [Gd(BO3)]∞ layer in the model structure Ba2Gd(BO3)2Cl. The magnetic measurements indicated that Ba2Gd(BO3)2F has a larger magnetocaloric effect with -ΔSm,max = 27.82 J·kg-1·K-1at 2 K and 9 T than that of Ba2Gd(BO3)2Cl under the same conditions. Moreover, thermal stability, infrared spectrum (IR), and ultraviolet-visible-near-infrared diffuse reflectance spectrum were carried out to characterize the title compounds. The first-principles computations also looked into the electronic band structures, densities of states, and refractive indices.