A prion-like domain in ELF3 functions as a thermosensor in Arabidopsis.

Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops1. However, the mechanisms by which plants sense temperature are not well understood. The evening complex is a major signalling hub and a core component of the plant circadian clock2,3. The evening complex acts as a temperature-responsive transcriptional repressor, providing rhythmicity and temperature responsiveness to growth through unknown mechanisms2,4-6. The evening complex consists of EARLY FLOWERING 3 (ELF3)4,7, a large scaffold protein and key component of temperature sensing; ELF4, a small α-helical protein; and LUX ARRYTHMO (LUX), a DNA-binding protein required to recruit the evening complex to transcriptional targets. ELF3 contains a polyglutamine (polyQ) repeat8-10, embedded within a predicted prion domain (PrD). Here we find that the length of the polyQ repeat correlates with thermal responsiveness. We show that ELF3 proteins in plants from hotter climates, with no detectable PrD, are active at high temperatures, and lack thermal responsiveness. The temperature sensitivity of ELF3 is also modulated by the levels of ELF4, indicating that ELF4 can stabilize the function of ELF3. In both Arabidopsis and a heterologous system, ELF3 fused with green fluorescent protein forms speckles within minutes in response to higher temperatures, in a PrD-dependent manner. A purified fragment encompassing the ELF3 PrD reversibly forms liquid droplets in response to increasing temperatures in vitro, indicating that these properties reflect a direct biophysical response conferred by the PrD. The ability of temperature to rapidly shift ELF3 between active and inactive states via phase transition represents a previously unknown thermosensory mechanism.

STAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to promote tumor growth.

SCAP plays a central role in controlling lipid homeostasis by activating SREBP-1, a master transcription factor in controlling fatty acid (FA) synthesis. However, how SCAP expression is regulated in human cancer cells remains unknown. Here, we revealed that STAT3 binds to the promoter of SCAP to activate its expression across multiple cancer cell types. Moreover, we identified that STAT3 also concurrently interacts with the promoter of SREBF1 gene (encoding SREBP-1), amplifying its expression. This dual action by STAT3 collaboratively heightens FA synthesis. Pharmacological inhibition of STAT3 significantly reduces the levels of unsaturated FAs and phospholipids bearing unsaturated FA chains by reducing the SCAP-SREBP-1 signaling axis and its downstream effector SCD1. Examination of clinical samples from patients with glioblastoma, the most lethal brain tumor, demonstrates a substantial co-expression of STAT3, SCAP, SREBP-1, and SCD1. These findings unveil STAT3 directly regulates the expression of SCAP and SREBP-1 to promote FA synthesis, ultimately fueling tumor progression.

The impact of lymphadenectomy on ovarian clear cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients. METHODS: We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460). RESULTS: Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60-0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34-0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60-1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64-1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation. CONCLUSION: Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies.

Single-cell transcriptomics dissects epithelial heterogeneity in HPV+ cervical adenocarcinoma.

The intra- and intertumoral heterogeneity of epithelial cells in human papillomavirus (HPV+ ) cervical adenocarcinoma (CEAD) remains largely unknown. To investigate this issue, we performed single-cell RNA sequencing on 19 229 epithelial cells sorted from three tumor samples of three patients with HPV+ CEAD. Six epithelial subclusters (Epi1-Epi6) were identified that showed distinct gene expression. Among these, Epi1 and Epi4 had apparent tumor hallmarks and metabolic activities. Epi1 was highly enriched in hallmarks of hypoxia, IL2/STAT5 signaling, retinol metabolism, glycolysis, and arachidonic acid metabolism, while Epi4 was highly enriched in hallmarks of G2M checkpoint, E2F targets, DNA repair, PI3K/AKT/MTOR signaling, glycolysis, fatty acid degradation, TCA cycle, and glutathione metabolism. We also investigated intertumoral epithelial heterogeneity and found that Patient 1 was highly enriched for KRAS signaling and angiogenesis, while Patient 2 was highly enriched for epithelial-mesenchymal transition and TGF-ß signaling, and Patient 3 was highly enriched for hypoxia, DNA repair, G2M checkpoint, and E2F targets. Using single-cell RNA sequencing, we revealed the intra- and intertumoral heterogeneity of epithelial cells in HPV+ CEAD, providing insights into the importance of personalized treatment for patients with HPV+ CEAD.

Evolution of the point defects involved under the action of mechanical forces on mechanically machined fused silica surfaces.

Point defects with different species are concentrated on most mechanically machined fused silica optical surfaces with surface defects, which would sharply decrease the laser damage resistance under intense laser irradiation. Various point defects have distinct roles in affecting the laser damage resistance. Especially, the proportions of various point defects have not been identified, posing the challenge in relating the intrinsic quantitative relationship among various point defects. To fully reveal the comprehensive effect of various point defects, it is necessary to systematically explore the origins, evolution laws and especially the quantitative relationship among point defects. Herein, seven types of point defects are determined. The unbonded electrons in point defects are found to tend to be ionized to induce laser damage and there is a definite quantitative relationship between the proportions of oxygen-deficient point defects and that of peroxide point defects. The conclusions are further verified based on the photoluminescence (PL) emission spectra and the properties (e.g., reaction rule and structural feature) of the point defects. On basis of the fitted Gaussian components and electronic-transition theory, the quantitative relationship between PL and the proportions of various point defects is constructed for the first time. E'-Center accounts for the highest proportion among them. This work is beneficial for fully revealing the comprehensive action mechanisms of various point defects and providing new insights in elucidating the defect-induced laser damage mechanisms of optical components under intense laser irradiation from the atomic scale.

Formation mechanism of DKDP surface in single point diamond fly-cutting process and the resulting degradation of laser-induced damage performance.

Laser damage performance of DKDP (KD2xH2(1-x)PO4) crystal is largely determined by the surface microstructures generated in the manufacturing process, more specifically, single point diamond fly-cutting process. However, because of the lack of knowledge about the formation mechanism and damage performance of the microstructures, laser induced damage of DKDP crystal remains a key issue limiting the output energy of the high power laser systems. In this paper, the influence of fly-cutting parameters on the generation of DKDP surface and the underlying material deformation mechanism have been investigated. Except for cracks, two kinds of new microstructures, namely micro grains and ripples, have been found on the processed DKDP surfaces. GIXRD, nano-indentation and nano-scratch test results prove that the micro grains are generated by the slip motion of the crystal, while the simulation results show that the cracks are induced by the tensile stress formed behind the cutting edge. Moreover, the formation of micro grains can facilitate the plastic chip flow through the mechanism of grain boundary sliding, which will further lead to a periodic fluctuation of the chip separation point and the formation of micro ripples. Finally, laser damage test results demonstrate that cracks will degrade the damage performance of DKDP surface significantly, while the formation of micro grains and micro ripples has little impact. The results of this study can deepen the understanding of the formation mechanism of the DKDP surface during the cutting process and provide guidance to improve the laser-induced damage performance of the crystal.

Evolution of intrinsic defects and ring structures on the surface of fused silica optics after CO2 laser conditioning.

Recently and interestingly, experiments show that the CO2 laser conditioning can significantly increase the laser-induced damage threshold (LIDT) of fused silica optics, but its underlying mechanism has not been clearly revealed. This Letter reports the experimental studies on the evolution of the intrinsic point defects and intrinsic ring structures on the surface of fused silica optics under the CO2 laser irradiation. The laser conditioning can effectively reduce the intrinsic defect contents in the surface layer of mechanically processed fused silica. However, the suppression effect of defects can be affected by the initial surface state. If there are micro-cracks on the component surface, the effect of the laser conditioning would be limited. The evolution of the intrinsic ring structures indicate that most of the intrinsic defects tend to recombine as short (Si-O)n ring structures during the laser healing of the micro-fractures. The observed recombination behavior and suppression of the intrinsic defects can help find out the reason for the increase of the LIDT of the fused silica optics.

Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma.

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.

Analysis of the dynamic changes in gut microbiota in patients with different severity in sepsis.

BACKGROUND: The gastrointestinal tract contains a massive microbiota, and targeting the gut could be a potential intervention for sepsis. However, the interaction between sepsis and the intestinal microbiota is defined as an "incompletely understood bidirectional relationship". METHODS: This retrospective observational cohort study investigated the fecal microbiota of sepsis patients admitted to the Department of Critical Care Medicine of the Central Hospital of Wuhan, China, from May 2019 to January 2020. 14 septic patients were divided into the non-severe group and the severe group according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Herein, fecal samples were serially collected on admission, the third, fourth, and fifth days, and ICU discharge. The fecal microbiota was analyzed by 16S rRNA gene sequencing and its correlation with clinical parameters was evaluated. RESULTS: Bacteroidetes, Firmicutes, and Proteobacteria were dominant phyla at ICU admission, and fecal biodiversity was not significantly different between the non-severe group (APACHE II < 15) and the severe group (APACHE II > 15). However, the diversity of the gut microbiota was significantly lower at ICU discharge than that at ICU admission with the extension of treatment time. Further significant difference flora analysis (LEfSe) showed that the genera Veillonella and Ruminococcus were the most discriminant biomarkers at ICU admission in non-severe and severe patients, respectively, while Enterococcus was the most discriminant biomarker at ICU discharge in all septic patients. Of note, liver function tests, including ALT, AST, TBIL, and DBIL correlated with the prevalence of various bacterial genera. CONCLUSIONS: The diversity of the gut microbiota in patients with sepsis decreases dramatically during ICU stay, and there are distinct dynamic changes in gut microbiota among patients with different severity in sepsis.

Label-free analysis of biofilm phenotypes by infrared micro- and correlation spectroscopy.

The methodology development for deeply describing the complex biofilm phenotypes is an urgent demand for understanding their basic biology and the central clinic relevance. Here, we developed an infrared microspectroscopy-based method for the quantitative evaluation and description of biofilm phenotypic characteristics by calculating the spectral similarity of the infrared data. Using this approach, we revealed the phenotypic variation during the biofilm formation process and biofilm heterogeneity between two E. coli strains. Two-dimensional correlation spectroscopy was further combined to deeply investigate the biochemical component evolution sequences during E. coli biofilm formation and revealed the first-order of the polysaccharide molecules change, expanding new opportunities for infrared microspectroscopy in revealing molecule evolution in the biofilm formation. This novel development offers a label-free optical toolkit for the bioanalytical analysis of biofilm phenotypes but also paves the way for screening the drugs to modulate the structure and ecology of biofilm microbiome.

Factors Associated With Utilization of Electroconvulsive Therapy During Psychiatric Hospitalization Among Children and Adolescents in China.

PURPOSE: Based on a nationally representative sample in China, we examined the demographic and clinical correlates of utilization of electroconvulsive therapy (ECT) in child and adolescent (C/A) patients younger than 18 years during psychiatric hospitalization. METHODS: As part of a national survey, 41 provincial tertiary psychiatric hospitals in mainland China were selected. Data from 196 C/A patients who were discharged from these psychiatric hospitals from March 19 to 31, 2019, were retrieved and analyzed. RESULTS: (1) The overall rate of ECT among C/A patients during psychiatric hospitalization was 15.6% (n = 30). (2) Between ECT and non-ECT groups, significant differences were found in sex, age, length of stay, Global Assessment of Functioning at admission, treatment outcome, and self-injurious behavior during hospitalization, and the ratio of marked improvement on discharge. (3) Multiple logistic regression analysis revealed that ECT use was independently and positively associated with an older age, male sex, lower Global Assessment of Functioning, and self-injurious behavior during hospitalization. CONCLUSIONS: The frequency of ECT use was relatively frequent in C/A patients during psychiatric hospitalization in our nationally representative sample in China. Developing more specific and operational criteria for the use of ECT for C/A patients is needed to provide guidance for the optimal use of ECT in this patient population.

Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

Membrane phosphatidylserine allosterically regulates the cytosolic phospholipase A2 activity via an electrostatic-switch mechanism.

Phospholipase A2 (PLA2) is a peripheral membrane protein that plays an essential role in many inflammatory responses. However, the activation mechanisms of PLA2 on the membrane surface have not been fully understood. Herein, we have combined experimental techniques and theoretical approaches to investigate the activation and association of the PLA2 protein on an artificial phospholipid membrane. Using a phosphatidylserine (PS) nanodomain containing membrane to mimic the inflammatory conditions, we found that the activity of cytosolic PLA2s (cPLA2s) increases with higher ratios of PS in the membrane. Molecular dynamics simulations reveal that significant changes in the protein structure are related to negatively charged membranes. In particular, the alteration of negatively charged residues in the C2 domain brings about an opened binding pocket and the catalytic site access to the substrate phospholipid. Meanwhile, the negative residues in the loop 650-665 facilitate the optimal interfacial orientation of the protein with a closed binding pocket on the membrane surface. These results lead us to suggest an electrostatic-switch allosteric mechanism for cPLA2 activation on the cell membrane surface under the inflammatory state.

Social Exclusion and Depression among undergraduate students: the mediating roles of rejection sensitivity and social self-efficacy.

Nowadays, depression has been a prominent mental health problem throughout the world. A common but negative social experience, social exclusion (also known as ostracism) is a great risk factor for individuals' health and adaptation. Undergraduate students are in a development period of challenges and transitions, so they are vulnerable to suffering from depression and negative social experiences. Against this background, the present study aimed to examine the association between social exclusion and undergraduate students' depression as well as the underlying mechanism - the mediating roles of rejection sensitivity and social self-efficacy. Seven hundred sixty-two undergraduate students were recruited to participate in this study, who were asked to complete a set of questionnaires measuring social exclusion, depression, rejection sensitivity, and social self-efficacy. After controlling for gender, social exclusion was positively associated with undergraduate students' depression. And rejection sensitivity and social self-efficacy could significantly mediate this relation through three mediating paths - the separate mediating effects of rejection sensitivity and social self-efficacy, as well as the serial mediating effect of rejection sensitivity and social self-efficacy. These results could not only deepen our understanding of this theme, but also have several practical implications for the intervention of depression, for example, relevant social skill training and cognitive therapy could be adopted to intervene the rejection sensitivity and social self-efficacy.

Formation mechanism of bubbles in the crack healing process of fused silica using a CO2 laser.

The machining-induced cracks and other defects on the surface of fused silica would incur damage when irradiated by intense lasers, which greatly shortens the service life of the fused silica optical components. The high absorption coefficient of fused silica for far-infrared lasers makes it possible to use low-energy CO2 lasers to melt and heal micro defects on the surface, and hence improve its damage threshold under the service conditions of extremely intense laser. However, the air in the cracks may evolve into bubbles during the laser healing process, but the law of crack morphology evolution and the bubble formation mechanism have not been clearly revealed. In this work, a simulation model of the healing process of fused silica surface cracks under the effect of low-energy CO2 laser is established. Three bubble formation mechanisms (i.e., the uneven fluidity caused by temperature gradient, the collapse effect caused by inclined cracks, and the internal cracks) are identified based on the simulation results of cracks with various original morphologies and characteristic structural parameters. The simulated fused silica morphology is consistent with the results of the laser healing experiment. This work can provide theoretical guidance for the optimization of optical manufacturing parameters of fused silica, as well as the CO2 laser healing and polishing strategies.

Elevated Rates of Restraint and Seclusion in Child and Adolescent Psychiatric Inpatients in China and Their Associated Factors.

To investigate the rate of restraint and seclusion (R&S) use in child and adolescent psychiatric inpatients in China and to examine factors associated with use of these interventions. As part of an official national survey, 41 provincial tertiary psychiatric hospitals in China were selected. Data from 196 youth inpatients discharged from these hospitals from March 19 to 31, 2019 were retrieved and analyzed. (1) The overall rate of R&S was 29.1% (N = 57) and the rate of restraint was 28.6% (N = 56), and seclusion was 11.7% (N = 23) respectively. (2) Compared to patients who did not require R&S, those who required R&S were more likely to have been hospitalized on an involuntary basis, more likely to present with either manic symptoms or aggressive behavior as primary reason for admission, had more frequent aggressive behaviors during hospitalization, and had a significantly longer length of stay. (3) A logistic regression showed that aggressive behaviors during hospitalization was significantly associated with the use of R&S (OR = 21.277, p < 0.001), along with three other factors: manic symptoms as a reason for admission, involuntary admission and a lower GAF score at admission (all p < 0.01). The rate of R&S is dramatically higher in child and adolescent psychiatric hospitalizations in China compared to other regions. Targeted training of staff, development of precise operational guidelines for appropriate use of R&S, and strict oversight are urgently needed to minimize the inappropriate use of R&S in child and adolescent patients.

Managing Locally Excited and Charge-Transfer Triplet States to Facilitate Up-Conversion in Red TADF Emitters That Are Available for Both Vacuum- and Solution-Processes.

Developing red thermally activated delayed fluorescence (TADF) emitters for high-performance OLEDs is still facing great challenge. Herein, three red TADF emitters, pDBBPZ-DPXZ, pDTBPZ-DPXZ, and oDTBPZ-DPXZ, are designed and synthesized with same donor-acceptor (D-A) backbone with different peripheral groups attaching on the A moieties. Their lowest triplet states change from locally excited to charge transfer character leading to significantly enhance reverse intersystem crossing process. In particular, oDTBPZ-DPXZ exhibits efficient TADF feature and exciton utilization. It not only achieves an external quantum efficiency (EQE) of 20.1 % in red vacuum-processed OLED, but also realize a high EQE of 18.5 % in a solution-processed OLED, which is among the best results in solution-processed red TADF OLEDs. This work provides an effective strategy for designing red TADF molecules by managing energy level alignments to facilitate the up-conversion process and thus enhance exciton harvesting.

Psychiatric inpatient beds for youths in China: data from a nation-wide survey.

BACKGROUND: The development of child psychiatric services in China has been slow and very limited resources have been allocated to support its growth. This study set out to investigate the child and adolescent inpatient psychiatric resources currently available in top-tier psychiatric hospitals in China and the characteristics of youth patients hospitalized on an adult unit. METHODS: As part of an official national survey, 29 provincial tertiary psychiatric hospitals in China were selected. Data from 1975 inpatients discharged from these hospitals from March 19 to 31, 2019 were retrieved and analyzed. RESULTS: The mean number of youth psychiatric beds was 27.7 ± 22.9 in these hospitals and 6/29 hospitals had no youth beds. There were significantly more youth beds in developed regions than in less developed regions (P < 0.05). Most of the discharged youth patients were teenagers with severe mental illnesses, including schizophrenia, depressive disorder and bipolar disorder. 7.5% (149) of the 1975 discharged patients were children or adolescents, however youth beds only accounted for 3.2% (804/25,136) of all psychiatric beds. 45.6% (68) of youth patients were discharged from adult psychiatric units. CONCLUSION: Our findings highlight the lack of adequate youth psychiatric inpatient services for children and adolescents living in China, especially in less developed regions. There is an urgent need to build more child and adolescent psychiatric units in provinces where there are none, and to increase the number of beds within the units that exist presently.

Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms.

BACKGROUND: Schizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype. METHODS: A total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1-4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2. RESULTS: Overall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly. CONCLUSION: We found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms. TRIAL REGISTRATION: This study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044 ).

Effect of laser pulse duration and fluence on DKDP crystal laser conditioning.

The impact of laser conditioning (LC) fluence and pulse duration on nanosecond (ns) laser damage performance of deuterated potassium dihydrogen phosphate (DKDP) crystal is studied. The result shows that higher LC fluence leads to a better damage resistance. In general, the sub-nanosecond LC effect is better than the nanosecond LC. However, in the range of 0.3 ns to 0.8 ns, the pulse duration has no obvious impact on the LC effect. An ultra-fast process characterization technology is employed to demonstrate that the cleaning effect of the protuberance defects on the surface is one of sub-ns LC mechanism. Eventually, a couple of optimized LC parameters that doubled the maximum damage threshold of DKDP crystal is proposed.