Intramolecular boron-locking strategy induced remarkable first hyperpolarizability: role of torsion angles between donor and acceptor units.

In conventional strategies to design donor-acceptor (D-A) organic molecules with a large electronic contribution to the first hyperpolarizability (ß), the effects of the torsion angles (θ1 and θ2) between donor and acceptor moieties are barely considered. To address this issue, in this work, a promising and novel intramolecular boron-locking strategy combined with the different locking groups of different acceptors to control θ1 and θ2, has been proposed to make D-A organic molecules with large ß values. Intriguingly, reducing the torsion angles will make the ß value of the pyridiny thiophene triphenylamine unit (Py-Th-TPA) dramatically increase up to 94%, which is mainly ascribed to the smaller θ1 and θ2 leading to lower excited energy of the crucial excited state, and enhanced charge transfer (CT) from TPA to Py-Th moieties, and finally greatly increase the donor and acceptor part contributions to ß. Correlation between the difference, |θ1 - θ2| and ß, provides a large coefficient of determination, R2 = 0.78, which demonstrates that |θ1 - θ2| can be regarded as a potential descriptor for designing nonlinear optics (NLO) materials with D-A architecture. Clearly, we uncovered that θ1 and θ2 play a crucial role in the performance of NLO materials with D-A fragments.

The development of the QM/MM interface and its application for the on-the-fly QM/MM nonadiabatic dynamics in JADE package: Theory, implementation, and applications.

Understanding the nonadiabatic dynamics of complex systems is a challenging task in computational photochemistry. Herein, we present an efficient and user-friendly quantum mechanics/molecular mechanics (QM/MM) interface to run on-the-fly nonadiabatic dynamics. Currently, this interface consists of an independent set of codes designed for general-purpose use. Herein, we demonstrate the ability and feasibility of the QM/MM interface by integrating it with our long-term developed JADE package. Tailored to handle nonadiabatic processes in various complex systems, especially condensed phases and protein environments, we delve into the theories, implementations, and applications of on-the-fly QM/MM nonadiabatic dynamics. The QM/MM approach is established within the framework of the additive QM/MM scheme, employing electrostatic embedding, link-atom inclusion, and charge-redistribution schemes to treat the QM/MM boundary. Trajectory surface-hopping dynamics are facilitated using the fewest switches algorithm, encompassing classical and quantum treatments for nuclear and electronic motions, respectively. Finally, we report simulations of nonadiabatic dynamics for two typical systems: azomethane in water and the retinal chromophore PSB3 in a protein environment. Our results not only illustrate the power of the QM/MM program but also reveal the important roles of environmental factors in nonadiabatic processes.

On-the-fly simulation of time-resolved fluorescence spectra and anisotropy.

We combine on-the-fly trajectory surface hopping simulations and the doorway-window representation of nonlinear optical response functions to create an efficient protocol for the evaluation of time- and frequency-resolved fluorescence (TFRF) spectra and anisotropies of the realistic polyatomic systems. This approach gives the effective description of the proper (e.g., experimental) pulse envelopes, laser field polarizations, and the proper orientational averaging of TFRF signals directly from the well-established on-the-fly nonadiabatic dynamic simulations without extra computational cost. To discuss the implementation details of the developed protocol, we chose cis-azobenzene as a prototype to simulate the time evolution of the TFRF spectra governed by its nonadiabatic dynamics. The results show that the TFRF is determined by the interplay of several key factors, i.e., decays of excited-state populations, evolution of the transition dipole moments along with the dynamic propagation, and scaling factor of the TFRF signals associated with the cube of emission frequency. This work not only provides an efficient and effective approach to simulate the TFRF and anisotropies of realistic polyatomic systems but also discusses the important relationship between the TFRF signals and the underlining nonadiabatic dynamics.

Speckle noise suppression method in a holographic display based on pixel processing.

In this paper, we propose a method to suppress the speckle noise in a holographic display based on pixel processing. Through the separation of object pixels in space, the recorded object is divided into multiple object point groups. The complex amplitude of the light field for each object point group is recorded as a sub-computer-generated hologram (sub-CGH). The phase of each pixel on a sub-CGH is optimized to generate the final sub-CGH. Therefore, the pixels of the recorded object and sub-CGH are processed. In the reconstruction process, the final sub-CGHs are loaded on the spatial light modulator sequentially. The speckle noise of the reconstructed image is suppressed by reducing the algorithm error and the overlapping area of adjacent image points. The experimental results prove the feasibility of the proposed method.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion.

BACKGROUND AND AIMS: The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI. METHODS: From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0. RESULTS: Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed. CONCLUSIONS: Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

A Practical Risk Classification of Early Recurrence in Hepatocellular Carcinoma Patients with Microvascular invasion after Hepatectomy: A Decision Tree Analysis.

PURPOSE: This study was designed to establish risk classifications for early recurrence in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. METHODS: The data of 563 HCC patients with MVI after hepatectomy from two hospitals were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse early recurrence. The risk classification for early recurrence was established by using classification and regression tree (CART) analysis and validated by using two independent validation cohorts from two hospitals. RESULTS: Multivariate analysis revealed that four indices, namely, infection of chronic viral hepatitis, MVI classification, tumour size, and serum alpha-fetoprotein (AFP), were independent prognostic factors for early recurrence in HCC patients with MVI. By CART analysis, MVI classification and serum AFP became the nodes of a decision tree and 3-stratification classifications that satisfactorily determined the risk of early recurrence were established. The area under the time-dependent receiver operating characteristic curve (AUC) values of the classification for early recurrence at 0.5, 1.0, and 2.0 years were 0.75, 0.73, and 0.71, respectively, which were all significantly higher than three common classic HCC stages (BCLC stage, Chinese stage, and TNM stage). The calibration curves showed good agreement between predictions by classification for early recurrence and actual survival outcomes. These prediction results also were confirmed in the independent internal and external validation cohorts. CONCLUSIONS: The 3 stratification classifications enabled satisfactory risk evaluation of early recurrence in HCC patients with MVI after hepatectomy.

Torsion Angles between Donor and Acceptor Moieties as a Descriptor for Designing Nonlinear Optics and Thermally Activated Delayed Fluorescence Materials.

The performances of nonlinear optics (NLO) and thermally activated delayed fluorescence (TADF) materials are strongly related to the torsion angles (θ) between donor (D) and acceptor (A) moieties in D-A architecture molecules. However, the underlying relationships connecting θ to the performances of NLO/TADF materials remain unclear. Herein, we present a comprehensive theoretical study on NLO/TADF materials composed of a series of D-A backbone molecules (TPAAP/TPAAQ series and AQ-DMAC/AQ-MeFAC series) to shed light on these relationships. It is found that changing θ via the intramolecular locking strategy can greatly influence values of the first hyperpolarizability (ß) and singlet-triplet energy gap (ΔEST), further leading to better/worse performances of NLO/TADF materials, respectively. Intriguingly, a more detailed analysis indicates that the variation trends between θ and ß/ΔEST are changeable in low θ regions, exhibiting volcano-like relationships. The large coefficients of determination (R2, ranging from 0.76 to 0.93) suggest that this experimentally measurable parameter (θ) can be used as a promising descriptor to evaluate the performances of related materials. Following the revealed θ-ß/θ-ΔEST correlations, the optimal/worst torsion angles for different materials are identified. These findings highlight the importance of the intrinsic structure-performance relationships, thus providing novel design strategies for high-performance NLO/TADF materials.

Positive associations between sex hormones, bone metabolism and cognitive impairment in Chinese oldest-old females.

PURPOSE: With a rapid increase in older adults, progressive impairment in cognitive function has become an increasing concern owing to high social and economic burdens. The current study was designed to investigate the associations of sex hormones and bone metabolism with cognitive impairment (CI) in Chinese oldest-old females. METHODS: There were 396 oldest-old females from the China Hainan Oldest-old Cohort Study (CHOCS). Following standardized procedures, Mini Mental State Examination was effectively completed, and sex hormones and bone metabolism were assessed in these females. RESULTS: The median age of all females was 101 years (range: from 80 to 116). There were 340 females (86%) with CI. Participants with CI had significantly higher levels of age, progesterone, prolactin and estradiol than those without CI (P < 0.05 for all). Total type I collagen N-terminal elongation peptide [hazard ratio (HR): 1.018, 95%CI: 1.001-1.035] and prolactin (HR: 1.065, 95%CI: 1.005-1.129) levels were positively and significantly associated with CI (P < 0.05 for all). CONCLUSIONS: Prolactin and total type I collagen N-terminal elongation peptide had positive associations with CI in Chinese oldest-old females. Thus, a balance in sex hormones and bone metabolism may have significant effects on cognitive function during the aging process.

Comparison of the plantar pressure distribution and mechanical alignment in patients with varus knee osteoarthritis following high tibial osteotomy.

PURPOSE: The changes in the lower limb alignment were vitally important after high tibial osteotomy (HTO). Therefore, the purpose of present study was to analyze the characteristics of plantar pressure distribution after HTO, and to investigate the effect of plantar pressure distribution on postoperative limb alignment. METHODS: Between May 2020 and April 2021, varus knee patients undergoing HTO were evaluated in the present study. The peak pressure of plantar regions, medial-lateral pressure ratio (MLPR), foot progression angle (FTA), anteroposterior COP (AP-COP), lateral symmetry of COP (LS-COP), and the radiographic parameters were evaluated preoperatively and at the final follow-up. Compared among the slight valgus (SV), moderate valgus (MV) and large valgus (LV) groups at the final follow-up, the peak pressure of HM, HC and M5 regions, and the MLPR were compared; the Knee Injury and Osteoarthritis Outcome Score4 (KOOS4) including four subscales, and the American of orthopedic foot and ankle society (AOFAS) were evaluated. RESULTS: The WBL%, HKA and TPI angle changed significantly after HTO (P < 0.001). The preoperative group exhibited a lower peak pressure in the HM region (P < 0.05) and higher peak pressure in the M5 region (P < 0.05); the pre- and postoperative groups exhibited a lower peak pressure in the HC region (P < 0.05); the rearfoot MLPR was significantly lower and LS-COP was significantly higher in the preoperative group (P = 0.017 in MLPR and 0.031 in LS-COP, respectively). Comparison among the SV, MV and LV groups, the SV group indicated a lower peak pressure in the HM region (P = 0.036), and a lower MLPR in the rearfoot (P = 0.033). The KOOS Sport/Re score in the MV and LV groups increased significantly compared with the SV group (P = 0.042). CONCLUSION: Plantar pressure distribution during the stance phase in patients with varus knee OA following HTO exhibited a more medialized rearfoot plantar pressure distribution pattern than that before surgery. Compared with the small valgus alignment, a moderate to large valgus alignment allows patients to walk with a more even medial and lateral plantar pressure distribution, which is more similar to healthy adults.

Genetic variation in the OPN gene affects milk composition in Chinese Holstein cows.

The aim of this study was to investigate the association between genotypes and haplotypes of OPN, and milk composition in dairy cows. A total of 317 Chinese Holstein cows were genotyped via DNA sequencing in this study. Three single nucleotide polymorphisms (SNPs), g.2916G > A, g.58675C > T and g.58899C > A, and eight haplotypes were identified. Of the eight possible haplotypes, four haplotypes i.e., Hap2 (ACC; 55.30%), Hap6 (GCC, 15.6%), Hap1 (ACA, 13.6%) and Hap4 (ATC, 5.70%), were considered to be major with a cumulative estimated frequency of >90%. Single markers (g.2916G > A and g.58899C > A) and Haplotype Hap6/4 were found to be associated with an increase in butter-fat percentage (p < 0.05). Taken together, our results provided evidence that polymorphisms in OPN are associated with milk composition, and could potentially be used for marker-assisted selection in Chinese Holstein cows.

[Prevention and treatment of lung cancer by regulating tumor-associated macrophages with traditional Chinese medicine].

Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.

Elevated NRAS expression during DCIS is a potential driver for progression to basal-like properties and local invasiveness.

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers. METHODS: Wilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS mRNA levels were also determined by fluorescence in situ hybridization in patient tumor microarrays (TMAs) with concurrent normal, DCIS, and invasive breast cancer, and association of NRAS mRNA levels with DCIS and invasive breast cancer was assessed by paired Wilcoxon signed-rank test. Pearson's correlation was calculated between NRAS mRNA levels and basal biomarkers in the TMAs, as well as in patient datasets. RNA-seq data were generated in cell lines, and unsupervised hierarchical clustering was performed after combining with RNA-seq data from a previously published patient cohort. RESULTS: Invasive breast cancers showed higher NRAS mRNA levels compared to DCIS samples. These NRAShigh lesions were also enriched with basal-like features, such as basal gene expression signatures, lower ER, and higher p53 protein and Ki67 levels. We have shown previously that NRAS drives aggressive features in DCIS-like and basal-like SUM102PT cells. Here, we found that NRAS-silencing induced a shift to a luminal gene expression pattern. Conversely, NRAS overexpression in the luminal DCIS SUM225 cells induced a basal-like gene expression pattern, as well as an epithelial-to-mesenchymal transition signature. Furthermore, these cells formed disorganized mammospheres containing cell masses with an apparent reduction in adhesion. CONCLUSIONS: These data suggest that elevated NRAS levels in DCIS are not only a marker but can also control the emergence of basal-like features leading to more aggressive tumor activity, thus supporting the therapeutic hypothesis that targeting NRAS and/or downstream pathways may block disease progression for a subset of DCIS patients with high NRAS.

Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization.

OBJECTIVES: Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS: A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS: Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS: ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS: • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.

The impact of different geometrical restrictions on the nonadiabatic photoisomerization of biliverdin chromophores.

The photoisomerization mechanism of the chromophore of bacterial biliverdin (BV) phytochromes is explored via nonadiabatic dynamics simulation by using the on-the-fly trajectory surface-hopping method at the semi-empirical OM2/MRCI level. Particularly, the current study focuses on the influence of geometrical constrains on the nonadiabatic photoisomerization dynamics of the BV chromophore. Here a rather simplified approach is employed in the nonadiabatic dynamics to capture the features of geometrical constrains, which adds mechanical restrictions to the specific moieties of the BV chromophore. This simplified method provides a rather quick approach to examine the influence of geometrical restrictions on photoisomerization. As expected, different constrains bring distinctive influences on the photoisomerization mechanism of the BV chromophore, giving either strong or minor modification of both involved reaction channels and excited-state lifetimes after the constrains are added in different ring moieties. These observations not only contribute to the primary understanding of the role of the spatial restriction caused by biological environments in photoinduced dynamics of the BV chromophore, but also provide useful ideas for the artificial regulation of the photoisomerization reaction channels of phytochrome proteins.

An intramolecular-locked strategy for designing nonlinear optical materials with remarkable first hyperpolarizability.

To meet the expanding demands of high performance nonlinear optical (NLO) materials, an unprecedented intramolecular-locked strategy is proposed to design NLO materials with remarkable static first hyperpolarizability (ß0). This strategy means that importing a large steric hindrance group diphenylmethane (DPM) decreases the torsion angles (θ) between the donor {triphenylamine (TPA)} and acceptor {9-H-thioxanthen-9-one-10,10-dioxide (TXO)} units, as well as between the donor (TPA) and π-bridge (benzene) fragments. The decrease of θ can accelerate the intramolecular charge transfer and enhance the contributions of the TPA, TXO and quinoxaline-6,7-dicarbo-nitrile (QCN) fragments to the axial component of the ß0 value, and then the ß0 values of TPA-TXO (ß0 = 10 762 au) and TPA-QCN (ß0 = 22 495 au) are increased by 14.9% and 34.4%, respectively. Overall, the intramolecular-locked strategy is very effective for designing high performance NLO materials.

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness.

OBJECTIVES: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. METHODS: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. RESULTS: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. CONCLUSION: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.

Roles for c-Abl in postoperative neurodegeneration.

The nonreceptor tyrosine kinase c-Abl is inactive under normal conditions. Upon activation, c-Abl regulates signaling pathways related to cytoskeletal reorganization. It plays a vital role in modulating cell protrusion, cell migration, morphogenesis, adhesion, endocytosis and phagocytosis. A large number of studies have also found that abnormally activated c-Abl plays an important role in a variety of pathologies, including various inflammatory diseases and neurodegenerative diseases. c-Abl also plays a crucial role in neurodevelopment and neurodegenerative diseases, mainly through mechanisms such as neuroinflammation, oxidative stress (OS), and Tau protein phosphorylation. Inhibiting expression or activity of this kinase has certain neuroprotective and anti-inflammatory effects and can also improve cognition and behavior. Blockers of this kinase may have good preventive and treatment effects on neurodegenerative diseases. Cognitive dysfunction after anesthesia is also closely related to the abovementioned mechanisms. We infer that alterations in the expression and activity of c-Abl may underlie postoperative cognitive dysfunction (POCD). This article summarizes the current understanding and research progress on the mechanisms by which c-Abl may be related to postoperative neurodegeneration.

Efficacy and safety of different options for liver regeneration of future liver remnant in patients with liver malignancies: a systematic review and network meta-analysis.

BACKGROUND: Several treatments induce liver hypertrophy for patients with liver malignancies but insufficient future liver remnant (FLR). Herein, the aim of this study is to compare the efficacy and safety of existing surgical techniques using network meta-analysis (NMA). METHODS: We searched PubMed, Web of Science, and Cochrane Library from databases for abstracts and full-text articles published from database inception through Feb 2022. The primary outcome was the efficacy of different procedures, including standardized FLR (sFLR) increase, time to hepatectomy, resection rate, and R0 resection margin. The secondary outcome was the safety of different treatments, including the rate of Clavien-Dindo≥3a and 90-day mortality. RESULTS: Twenty-seven studies, including three randomized controlled trials (RCTs), three prospective trials (PTs), and twenty-one retrospective trials (RTs), and a total number of 2075 patients were recruited in this study. NMA demonstrated that the Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) had much higher sFLR increase when compared to portal vein embolization (PVE) (55.25%, 95% CI 45.27-65.24%), or liver venous deprivation(LVD) (43.26%, 95% CI 22.05-64.47%), or two-stage hepatectomy (TSH) (30.53%, 95% CI 16.84-44.21%), or portal vein ligation (PVL) (58.42%, 95% CI 37.62-79.23%). ALPPS showed significantly shorter time to hepatectomy when compared to PVE (-32.79d, 95% CI -42.92-22.66), or LVD (-34.02d, 95% CI -47.85-20.20), or TSH (-22.85d, 95% CI -30.97-14.72), or PVL (-43.37d, 95% CI -64.11-22.62); ALPPS was considered as the highest resection rate when compared to TSH (OR=6.09; 95% CI 2.76-13.41), or PVL (OR =3.52; 95% CI 1.16-10.72), or PVE (OR =4.12; 95% CI 2.19-7.77). ALPPS had comparable resection rate with LVD (OR =2.20; 95% CI 0.83-5.86). There was no significant difference between them when considering the R0 marge rate. ALPPS had a higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments, although there were no significant differences between different procedures. CONCLUSIONS: ALPPS demonstrated a higher regeneration rate, shorter time to hepatectomy, and higher resection rate than PVL, PVE, or TSH. There was no significant difference between them when considering the R0 marge rate. However, ALPPS developed the trend of higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments.

Tuning the first hyperpolarizability of hexaphyrins with different connections of mislinked pyrrole units: a theoretical study.

In the satisfactory design and synthesis of high-performance nonlinear optical (NLO) materials, for meeting the rapidly expanding demands of optoelectronic devices, a deeper understanding of the relationship between the structures and NLO properties has become a key issue. Herein, five novel mislinked expanded hexaphyrins with different connections of pyrrole units are selected to study the relationship between the structures and NLO properties. These five mislinked expanded hexaphyrins are neo-fused, neo-confused hexaphyrins, singly, doubly, and triply N-confused hexaphyrins. From theoretical results, the order of the static first hyperpolarizability (ß0) values is found to be: neo-fused hexaphyrin (ß0 = 4163 a.u.) < neo-confused hexaphyrin (ß0 = 5494 a.u.) < singly N-confused hexaphyrin (ß0 = 6510 a.u.) < doubly N-confused hexaphyrin (ß0 = 15 130 a.u.) < triply N-confused hexaphyrin (ß0 = 26 095 a.u.). Furthermore, ß0 values of the doubly and triply N-confused hexaphyrins are improved 2.1 and 3.7 times over that of their usual parent hexaphyrin (ß0 = 7120 a.u.), respectively. It is worth noting that increasing mislinked connection numbers and changing mislinked connection ways of the pyrrole units in these mislinked expanded hexaphyrins plays a crucial role in the tune of their second-order NLO responses.

Nonadiabatic molecular dynamics simulation for the ultrafast photoisomerization of dMe-OMe-NAIP based on TDDFT on-the-fly potential energy surfaces.

Global switching on-the-fly trajectory surface hopping molecular dynamics simulation was performed on the accurate TD-B3LYP/6-31G* potential energy surfaces for E-to-Z and Z-to-E photoisomerization of dMe-OMe-NAIP up to S1(ππ*) excitation. The present TD(DFT) simulation provides accurate calculation for conical intersections between the first-excited and ground states. Thus, simulated quantum yield and lifetime of 0.23 and 620 fs (0.15 and 600 fs) for E-to-Z (Z-to-E) isomerization are in good (relatively good) agreement with experimental observation of 0.25 and 480 fs (0.24 and 430 fs), respectively. Simulated results reveal that photoisomerization pathways are initially uphill to conical intersection zones on the S1 potential energy surface and then downhill to product zones. Three types of representative conical intersections are found for determining photoisomerization mechanisms: one is the rotation type responsible for reactive isomerization and the other two are close to E and Z configurations, respectively, only for nonreactive isomerization. The present conclusions can be held in general for similar large NAIP systems of photoinduced isomerization based on E and Z configurations.