[Effects of unilateral thoracic paravertebal block on hemodynamic and the level of conscionsness during double lumen endotracheal intubation].

OBJECTIVE: To compare the effects of unilateral thoracic paravertebal block with lidocaine on hemodynamic and the level of consciousness during double lumen endotracheal intubation. METHODS: From June to october 2021, a total of 40 patients American Society of Anesthesiologists (ASA) physical status Ⅰ-Ⅱ, aged 19-65 years, scheduled for elective thoracic sugeries in Peking University International Hospital block with under general anesthesia requiring orotracheal intubation were recruited and divided into two groups: The double-lumen endobronchial intubation (group C) and double-lumen endobronchial intubation after thoracic paravertebal block with lidocaine (group P). After an intravenous anesthetic induction, the orotracheal double-lumen intubation was performed using a Macintosh direct laryngoscopy, respectively. Invasive blood pressure (BP) and heart rate (HR) were recorded before and after anesthetic induction, immediately after intubation and 5 min after intubation with 1-minute interval and the intubation time was also noted. Rate-pressure product (RPP) were calculated. RESULTS: After anesthetic induction, BP and RPP in the two groups decreased significantly compared with their preinduction values. As comparison with their postinduction values, the orotracheal intubation in the two groups caused significant increases in BP, HR and RPP. Diastolic blood pressure (DBP) and mean arterial pressure (MAP) increased significantly and lasted for 1-minute in group C compared with the baseline values. Systolic blood pressure (SBP) was not significant change and DBP increased significantly immediately after intubation in group P.HR of both groups after intubation were significantly higher than their baseline values and lasted for 4 min in group C, HR increased significantly immediately after intubation in group P. SBP, DBP, MAP, HR and RPP after intubation in group P were significantly lower than those of group C during the observation period. The value of BIS was similar between the two groups. Compared with group C, the incidence of SBP greater than 30% and RPP greater than 22 000 was significantly lower in group P in the observation period, and no patient in group P developed RPP greater than 22 000. At the end of the incidence of SBP less than 30% of the basal value and HR less than 30% of the baseline, no severe bradycardia occurred in both groups. CONCLUSION: During double-lumen endobronchial intubation, unilateral thoracic paravertebal block with lidocaine can provide less hemodynamic response and level of conscionsness.

Suppressing FXR promotes antiviral effects of bile acids via enhancing the interferon transcription.

Bile acids (BAs) are natural metabolites in mammals and have the potential to function as drugs against viral infection. However, the limited understanding of chenodeoxycholic acid (CDCA) receptors and downstream signaling, along with its lower suppression efficiency in inhibiting virus infection limits its clinical application. In this study, we demonstrate that farnesoid X receptor (FXR), the receptor of CDCA, negatively regulates interferon signaling, thereby contributing to the reduced effectiveness of CDCA against virus replication. FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection. Mechanistically, FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3 (IRF3) through interaction. Reduced IRF3 transcriptional activity by FXR-IRF3 interaction significantly undermines the expression of Interferon Beta 1 (IFNB1) and the antiviral response of cells, especially upon the CDCA treatment. In FXR-deficient cells, or when combined with Z-guggulsterone (GUGG) treatment, CDCA exhibits a more potent ability to restrict virus infection. Thus, these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication, which can be attributed to the "signaling-brake" roles of FXR in interferon signaling. Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.

TFCP2L1 drives stemness and enhances their resistance to Sorafenib treatment by modulating the NANOG/STAT3 pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy associated with high risks of recurrence and metastasis. Liver cancer stem cells (CSCs) are increasingly recognized as pivotal drivers of these processes. In our previous research, we demonstrated the involvement of TFCP2L1 in maintaining the pluripotency of embryonic stem cells. However, its relevance to liver CSCs remains unexplored. In this study, we report an inverse correlation between TFCP2L1 protein levels in HCC tissue and patient outcomes. The knockdown of TFCP2L1 significantly reduced HCC cell proliferation, invasion, metastasis, clonal formation, and sphere-forming capacity, while its overexpression enhanced these functions. In addition, experiments using a nude mouse model confirmed TFCP2L1's essential role in liver CSCs' function and tumorigenic potential. Mechanistically, we showed that TFCP2L1 promotes the stemness of CSCs by upregulating NANOG, which subsequently activates the JAK/STAT3 pathway, thereby contributing to HCC pathogenesis. Importantly, we identified a specific small molecule targeting TFCP2L1's active domain, which, in combination with Sorafenib, sensitizes hepatoma cells to treatment. Together, these findings underscore TFCP2L1's pathological significance in HCC progression, supporting its potential as a prognostic biomarker and therapeutic target in this disease.

Using ligand regulation, metal replacement, and ligand doping strategies on Zr-FUM to improve methane separation from coalbed gas.

Developing adsorbents suitable for industrial applications that can effectively enhance the separation of methane (CH4) from nitrogen (N2) in coalbed gas is crucial to improve energy recovery and mitigate greenhouse gas emissions. In this study, three modification strategies were implemented on Zr-FUM, including ligand regulation, metal replacement, and ligand doping, to synthesize Zr-FDCA, Al-FUM, and Zr-FUM-FA, with the aim of improving the performance of CH4/N2 separation under humid conditions. The results demonstrated that the promotion of robust orbital overlap and strengthened electrovalent bonding on adsorbents can selectively enhance CH4 adsorption. As a result, Zr-FUM-FA achieved a saturated CH4 adsorption capacity of 1.37 mmol/g, a CH4 working window of 307 s, and a CH4/N2 sorbent selection parameter (Ssp) of 47.31, exceeding the performance of most reported adsorbents. Analyses of the pore structure, surface morphology, and functional groups revealed that the presence of an ultramicropore proximity to CH4, reduced static resistance, and enhanced electrovalent bond were key factors for CH4 separation. Grand Canonical Monte Carlo and Density Functional Theory studies indicated that the introduction of -C-H- in FA played a crucial role in enhancing CH4 adsorption. Optimization of adsorption parameters using the Aspen adsorption package showed that in a dual-adsorbent bed system, the recovery and purity of CH4 in Zr-FUM-FA reach 99.5% and 97.3%, respectively, providing important theoretical support for the improvement of CH4 recovery in the pressure swing adsorption process from coalbed gas.

Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2.

The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

Total glucosides of paeony inhibit NLRP3/caspase-1/GSDMD-mediated inflammation and pyroptosis in C3H/HeJ alopecia areata mice.

One of the most prominent causes of alopecia areata (AA) is chronic inflammation of the hair follicles. Inhibiting cellular pyroptosis, a form of inflammatory programmed cell death, is crucial for reducing follicular inflammation in the skin. Total glucosides of paeony (TGP) possess anti-inflammatory properties across a broad range of illnesses. However, the role of TGP in AA and its relationship to pyroptosis remains unclear. A chronic unpredictable mild stress (CUMS) approach was used to create an AA mouse model. TGP suspension and MCC950 were administered to AA mice via gavage. HE staining, ELISA, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blotting were performed to detect pathological changes in the skin and to investigate the levels of inflammatory factors and pyroptosis-related proteins, as well as the potential mechanisms of TGP's effects. TGP reduced hair loss, increased the number of hair follicles in skin tissues, and decreased inflammatory markers (IL-6, TNF-α, IL-18, and IL-1ß) in AA mice. MCC950 significantly reduced the levels of NLRP3/caspase-1/GSDMD-mediated pyroptosis-related proteins (NLRP3, ASC, caspase-1 p10, and GSDMD-N), as well as inflammatory factors. TGP markedly inhibited NLRP3/caspase-1/GSDMD-mediated cellular pyroptosis in a concentration-dependent manner. TGP suppresses the NLRP3/caspase-1/GSDMD signaling cascade in the skin tissues of AA mice, thereby reducing cellular pyroptosis and inflammation. TGP may be a potential therapeutic agent for AA.

Study on the variation law of smoke layer thickness with ceiling structure height in long-narrow space with one end opening.

The ceiling structure in a long-narrow space has a significant impact on the thickness of the fire smoke layer. This paper mainly studies the influence of the height of the ceiling structure on the thickness of the smoke layer before the ceiling structure. Firstly, a theoretical analysis is conducted on the relationship between the critical thickness that affects the smoke flow state and the smoke layer thickness directly below the ceiling structure, and a formula for calculating the smoke layer thickness under gradient flow conditions is derived. Then a small-scale experimental platform was built to study the deviation of actual fire smoke relative to theoretical calculations. Experimental results show that due to the smoke cannot maintain gradient flow when crossing the ceiling structure, there is difference with theoretical calculations in the smoke layer thickness directly below the ceiling structure and some distance before the ceiling structure (which may be of greater concern for personnel evacuation). The gradient flow coefficient and thickness coefficient are defined to represent the above differences. After analysis, it was found that the gradient flow coefficient and thickness coefficient showed different linear variation patterns when the height of the ceiling structure was longer than 35 cm or shorter than 30 cm. Through numerical analysis, this study suggests that the main reason for the change in this linear pattern is whether the potential energy conversed from kinetic energy of the thin layer close to the ceiling structure can directly make the smoke to cross the ceiling structure. The research conclusions of this paper can assist in the engineering design of building smoke control and personnel evacuation.

Unveiling the Pharmacological Role of Human Deubiquitinating Enzymes in Temozolomide Response of Glioblastoma Cells.

Temozolomide (TMZ) stands as the primary chemotherapeutic drug utilized in clinical glioma treatment, particularly for high-grade glioblastoma (GBM). However, the emergence of TMZ resistance in GBM poses a significant hurdle to its clinical efficacy. Our objective was to elucidate the role of deubiquitinating enzymes (DUBs) in GBM cell resistance to TMZ. We employed the broad-spectrum DUBs inhibitor G5 to investigate the function of DUBs in TMZ cytotoxicity against GBM cells. Eighty-two GBM cell lines with specified DUBs knockout were generated and subjected to CCK-8 assays to assess cell proliferation and TMZ resistance. Furthermore, the association between DUBs and TMZ resistance in GBM cells, along with the modulation of autophagic flux, was examined. The pan-DUBs inhibitor G5 demonstrated the ability to induce cell death and enhance TMZ toxicity in GBM cells. Subsequently, we identified potential DUBs involved in regulating GBM cell proliferation and TMZ resistance. The impact of DUBs knockout on TMZ cytotoxicity was found to be associated with their regulation of TMZ-induced autophagy. In summary, our study provides primary insights into the role of DUBs in GBM cell proliferation and TMZ resistance, and contributes to a deeper understanding of the complex function of DUBs genes underlying TMZ resistance in GBM cells.

Activation of farnesoid X receptor enhances the efficacy of normothermic machine perfusion in ameliorating liver ischemia-reperfusion injury.

The shortage of transplant organs remains a severe global issue. Normothermic machine perfusion (NMP) has the potential to increase organ availability, yet its efficacy is hampered by the inflammatory response during machine perfusion. Mouse liver ischemia-reperfusion injury (IRI) models, discarded human liver models, and porcine marginal liver transplantation models were utilized to investigate whether farnesoid X receptor (FXR) activation could mitigate inflammation-induced liver damage. FXR expression levels before and after reperfusion were measured. Gene editing and coimmunoprecipitation techniques were employed to explore the regulatory mechanism of FXR in inflammation inhibition. The expression of FXR correlates with the extent of liver damage after reperfusion. Activation of FXR significantly suppressed the inflammatory response triggered by IRI, diminished the release of proinflammatory cytokines, and improved liver function recovery during NMP, assisting discarded human livers to reach transplant standards. Mechanistically, FXR disrupts the interaction between p65 and p300, thus inhibiting modulating the nuclear factor kappa-B signaling pathway, a key instigator of inflammation. Our research across multiple species confirms that activating FXR can optimize NMP by attenuating IRI-related liver damage, thereby improving the utilization of marginal livers for transplantation.

Anesthetic managements, morbidities and mortalities in retroperitoneal sarcoma patients experiencing perioperative massive blood transfusion.

Objective: Given high risks of major bleeding during retroperitoneal sarcoma(RPS) surgeries, severe complications and deaths are common to see perioperatively. Thus, effective anesthetic management is the key point to ensuring the safety of patients. This study aimed to introduce anesthesia management and mortalities in RPS patients receiving massive blood transfusions during surgeries. Methods: Records of RPS surgeries under general anesthesia from January 2016 through December 2021 were retrospectively retrieved from our database. Patients who received massive blood transfusions (MBT) exceeding 20 units in 24h duration of operations were finally included in this study. Demographics, modalities of anesthesia management, blood loss, transfusion, peri-anesthesia biochemical tests as well as morbidities and mortalities were collected. Risk factors of postoperative 60d mortality were determined through logistic regression in uni-and multi-variety analysis using the statistics software STATA 17.0. Results: A total of 70 patients (male 31) were included. The mean age was 50.1 ± 15.8 years. All patients received combined resections of sarcoma with involved organs under general anesthesia. Mean operation time and anesthesia time were 491.7 ± 131.1mins and 553.9 ± 132.6mins, respectively. The median intraoperative blood loss was 7000ml (IQR 5500,10000ml). Median red blood cells (RBC) and fresh frozen plasma (FFP) transfusion were 25.3u (IQR 20,28u), and 2400ml (IQR 2000,3000ml), respectively. Other blood products infusions included prothrombin complex concentrate (PCCs), fibrinogen concentrate (FC), platelet(plt) and albumin(alb) in 82.9% (58/70), 88.6% (62/70), 81.4% (57/70) and 12.9% (9/70) of patients. The postoperative severe complication rate(Clavien-Dindo grade≥3a) was 35.7%(25/70). A total of 7 patients (10%) died during the postoperative 60-day period. BMI, volumes of crystalloid infusion in anesthesia, and hemoglobin and lactate levels at the termination of operation were found significantly associated with postoperative occurrence of death in univariate analysis. In logistic multivariate analysis, extended anesthesia duration was found associated with postoperative venous thrombosis embolism (VTE) and severe complication. The lactate level at the immediate termination of the operation was the only risk factor related to perioperative death (p<0.05). Conclusion: RPS patients who endure MBT in surgeries face higher risks of death postoperatively, which needs precise and effective anesthesia management in high-volume RPS centers. Increased blood lactate levels might be predictors of postoperative deaths which should be noted.

Minimal alveolar concentration of sevoflurane in combination with remimazolam in adults during laryngeal mask insertion: an up-down sequential allocation study.

BACKGROUND: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative-hypnotic. The combination of remimazolam and sevoflurane does not increase respiratory sensitivity, produce bronchospasm, or cause other adverse conditions. We aimed to observe the effects of different remimazolam doses on the minimum alveolar concentration (MAC) of sevoflurane at end-expiration during laryngeal mask insertion and evaluate the effect of sex on the efficacy of the combination of remimazolam on the suppression of laryngeal mask insertion in adult patients. METHODS: We included 240 patients undergoing laparoscopic surgery under general anesthesia with elective placement of a laryngeal mask (120 males and 120 females). The patients were randomly divided into four groups according to sex: a control group (randomization for female patients, RF0; randomization for male patients, RM0) and three remimazolam groups (RF1, RM1 / RM2, RF2 / RM3, RF3), with 30 patients in each group. Induction was established by vital capacity rapid inhalation induction (VCRII), using 8% sevoflurane and 100% oxygen (6 L/min) in all patients. The (RF1, RM1), (RM2, RF2), and (RM3, RF3) groups were continuously injected with remimazolam at doses of 1, 1.5, and 2.0 mg/kg/h, respectively, while the (RM0, RF0) group was injected with an equal volume of normal saline. The end-expiratory concentration of sevoflurane was adjusted to a preset value after the patient's eyelash reflex disappeared. After the end-expiratory concentration of sevoflurane was kept stable for at least 15 min, the laryngeal mask was placed, and the patient's physical response to the mask placement was observed immediately and within 30 s of placement. The MAC of sevoflurane was measured using the up-and-down sequential method of Dixon. RESULTS: The calculated MAC of end-expiratory sevoflurane during laryngeal mask insertion in adult females was (2.94 ± 0.18)%, (2.69 ± 0.16)%, (2.32 ± 0.16)% and (1.83 ± 0.15)% in groups RF0, RF1, RF2 and RF3; (2.98 ± 0.18)%, (2.80 ± 0.19)%, (2.54 ± 0.15)% and (2.15 ± 0.15)% in male groups RM0, RM1, RM2 and RM3, respectively. The MAC values were significantly lower in the (RF1-RF3, RM1-RM3) group when compared to the (RF0, RM0) group. There was no significant difference between (RF0, RF1) and (RM0, RM1), but the MAC value of the RF2-RF3 group was significantly lower than that of the RM2-RM3 group. CONCLUSIONS: Remimazolam can effectively reduce end-expiratory sevoflurane MAC values during laryngeal mask placement in adults. When remimazolam was measured above 1.5 mg/kg/h, the effect of inhibiting laryngeal mask implantation in female patients was stronger than that in male patients. Remimazolam at a dose of 1-2 mg/kg/h combined with sevoflurane induction can be safely and effectively used in these patients.

Effectiveness of a broad-spectrum bivalent mRNA vaccine against SARS-CoV-2 variants in preclinical studies.

Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.

Histone Variant H3.3 Controls Arabidopsis Fertility by Regulating Male Gamete Development.

Reprograming of chromatin structures and changes in gene expression are critical for plant male gamete development, and epigenetic marks play an important role in these processes. Histone variant H3.3 is abundant in euchromatin and is largely associated with transcriptional activation. The precise function of H3.3 in gamete development remains unclear in plants. Here, we report that H3.3 is abundantly expressed in Arabidopsis anthers and its knockout mutant h3.3-1 is sterile due to male sterility. Transcriptome analysis of young inflorescence has identified 2348 genes downregulated in h3.3-1 mutant, among which 1087 target genes are directly bound by H3.3, especially at their 3' ends. As a group, this set of H3.3 targets is enriched in the reproduction-associated processes including male gamete generation, pollen sperm cell differentiation and pollen tube growth. The function of H3.3 in male gamete development is dependent on the Anti-Silencing Factor 1A/1B (ASF1A/1B)-Histone regulator A (HIRA)-mediated pathway. Our results suggest that ASF1A/1B-HIRA-mediated H3.3 deposition at its direct targets for transcription activation forms the regulatory networks responsible for male gamete development.

Conscious sedation anesthesia using different doses of remifentanil combined with dexmedetomidine for peritoneal dialysis catheter implantation.

BACKGROUND: Conscious sedation anesthesia (CSA) is an anesthetic method during peritoneal dialysis catheter implantation. However, lack of optimal CSA strategies for patients with end-stage renal disease (ESRD). This study aimed to evaluate the analgesic effects and safety of CSA using different doses of remifentanil combined with dexmedetomidine during peritoneal dialysis catheter insertion. METHODS: Patients who underwent peritoneal dialysis (PD) catheter placement via open surgical incision were retrospectively analyzed and divided into three groups based on the tertile dose of remifentanil. The bispectral index (BIS) was used to monitor the depth of anesthesia. Data regarding clinical findings, the effects of anesthesia, and the incidence of drug-related adverse effects were collected. RESULTS: In total, 102 patients completed the surgery successfully and safely. The dose of remifentanil was 0.02-0.07 µg/kg/min, 0.08-0.13 µg/kg/min, and 0.14-0.20 µg/kg/min in Groups A, B, and C, respectively. Only seven patients reported mild pain during the surgery. No significant differences were observed among the numeric rating scale scores of the three groups (p > 0.05). Intraoperative hemodynamics were stable. The incidence of respiratory depression was 8.3%, 20.0%, and 41.9% in Groups A, B, and C, respectively (p < 0.01). The incidence of gastrointestinal symptoms in Group C (51.6%) was higher than that in Groups A and B (p < 0.05). CONCLUSION: Low-dose remifentanil (0.02-0.07 µg/kg/min) combined with dexmedetomidine achieved satisfactory anesthetic effects with fewer adverse drug reactions during PD catheter implantation, indicating its potential for use in patients undergoing PD catheter placement.

The causal effects of leisure screen time on irritable bowel syndrome risk from a Mendelian randomization study.

Associations between leisure sedentary behavior (especially leisure screen time, LST) and irritable bowel syndrome (IBS) have been reported, but causality is unclear. Here, the two-sample Mendelian randomization was performed to investigate the causal association between LST and IBS. Two recently published genome-wide association studies (GWASs) including a total of 1,190,502 people from Europe were used as our data source. Inverse variance weighting (OR = 1.120, 95% CI 1.029-1.219) and weighted median (OR = 1.112, 95% CI 1.000-1.236) analyses revealed a causal effect between LST and IBS. There was no evidence of pleiotropy in the sensitive analysis (MR-Egger, p = 0.139). After removing potentially confounding single nucleotide polymorphisms (SNPs), similar results were found using inverse variance weighting (OR = 1.131, 95% CI 1.025-1.248) and weighted median (OR = 1.151, 95% CI 1.020-1.299), as well as in the validation analyses using inverse variance weighting (OR = 1.287, 95% CI 0.996-1.662). This study provided support for a possible causal relationship between leisure screen time and IBS.

Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma.

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

High-precision phase retrieval method for speckle suppression based on optimized modulation masks.

Traditional methods of coherent diffraction imaging using random masks result in an insufficient difference between the diffraction patterns, making it challenging to form a strong amplitude constraint, causing significant speckle noise in the measurement results. Hence, this study proposes an optimized mask design method combining random and Fresnel masks. Increasing the difference between diffraction intensity patterns enhances the amplitude constraint, suppresses the speckle noise effectively, and improves the phase recovery accuracy. The numerical distribution of the modulation masks is optimized by adjusting the combination ratio of the two mask modes. The simulation and physical experiments show that the reconstruction results of PSNR and SSIM using the proposed method are higher than those using random masks, and the speckle noises are effectively reduced.