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Qingqing Li,1,* Tong Su,2,* Xu Zhang,3,* Yanfeng Pan,1,* Shengli Ma,4 Lu Zhang,4 Xianqiang Zhang,1 Xiaojuan Gao1 1Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou city, People’s Republic of China; 2Department of Medical, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou city, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou city, People’s Republic of China; 4Department of Infectious Diseases, The People’s Hospital of Yongcheng, Yongcheng city, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanfeng Pan, Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Jinshui District, Zhengzhou city, 450000, People’s Republic of China, Tel +8613938448759, Email panfirstfeng@163.comPurpose: To observe the efficacy and safety of anlotinib as a first-line treatment for patients with advanced hepatocellular carcinoma (aHCC) in a real-word environment, explore the optimal treatment regimen for patients with aHCC using anlotinib as a first-line treatment.Patients and Methods: Data from 62 patients with aHCC who received anlotinib single-drug first-line therapy between February 2019 and November 2021. Patients received anlotinib monotherapy, which may be interrupted or discontinued or changed in the event of unacceptable or severe adverse events (AEs) or failure to inhibit tumor progression. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate(ORR), disease control rate (DCR), overall survival (OS), and safety.Results: Among the 62 patients, in the best overall response assessment, there were 12 with complete response (CR; 19.4%), 17 with partial response (PR; 27.4%), 25 with stable disease (SD; 40.3%), and 8 with progressive disease (PD; 14.5%). The ORR and DCR were 46.8% and 87.1%, respectively. Among the 11 patients who received tyrosine kinase inhibitors (TKIs) combined with programmed death 1 (PD-1) inhibitors after disease progression, three (27.3%) had CR, one (9.1%) had PR, three (27.3%) had SD, and four (36.4%) had PD. Therefore, the ORR and DCR were 36.4% and 63.6%, respectively. The median PFS for anlotinib monotherapy was 7.37 months (95% confidence interval [CI]: 5.88– 8.86) and the median OS did not reach. AEs occurred in 95.2% of patients during anlotinib monotherapy, with the most common being thrombocytopenia (51.6%). The incidence of grade ≥ 3 AEs was 38.7%.Conclusion: Anlotinib is effective and well-tolerated as a first-line treatment for patients with aHCC. Treatment with TKIs and PD-1 inhibitors after disease progression has also shown preliminary efficacy and safety; therefore, sequential therapy with anlotinib-TKIs and PD-1 inhibitors may be an effective treatment for patients with aHCC.Keywords: hepatocellular carcinoma, anlotinib, sequential therapy, real world

Cognitive dysfunction is a significant, untreated clinical need in patients with psychiatric disorders, for which preclinical studies are needed to understand the underlying mechanisms and to identify potential therapeutic targets. Early-life stress (ELS) leads to long-lasting deficits of hippocampus-dependent learning and memory in adult mice, which may be associated with the hypofunction of the brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB). In this study, we carried out eight experiments to examine the causal involvement of the BDNF-TrkB pathway in dentate gyrus (DG) and the therapeutic effects of the TrkB agonist (7,8-DHF) in ELS-induced cognitive deficits. Adopting the limited nesting and beding material paradigm, we first demonstrated that ELS impaired spatial memory, suppressed BDNF expression and neurogenesis in DG in adult mice. Down-regulating BDNF expression (conditional BDNF knockdown) or inhibition of the TrkB receptor (using its anatognist ANA-12) in the DG mimicked the cognitive deficits of ELS. Acute up-regulation of BDNF (exogenous human recombinant BDNF microinjection) levels or activation of TrkB receptor (using its agonist, 7,8-DHF) in the DG restored ELS-induced spatial memory loss. Finally, acute and subchronic systemic administration of 7,8-DHF successfully restored spatial memory loss in stressed mice. Subchronic 7,8-DHF treatment also reversed ELS-induced neurogenesis reduction. Our findings highlight BDNF-TrkB system as the molecular target of ELS-induced spatial memory deficits and provide translational evidence for the intervention at this system in the treatment of cognitive deficits in stress-related psychiatric disorders, such as major depressive disorder.

Background: Post-Traumatic Stress Disorder (PTSD) is a severe psychological disorder characterized by intrusive thoughts, heightened arousal, avoidance, and flashbacks. Cognitive flexibility dysfunction has been linked with the emergence of PTSD, including response inhibition deficits and impaired attentional switching, which results in difficulties for PTSD patients when disengaging attention from trauma-related stimuli. However, the molecular mechanisms of cognitive flexibility deficits remain unclear. Methods: The animals were exposed to a single prolonged stress and electric foot shock (SPS&S) procedure to induce PTSD-like features. Once the model was established, the changes in cognitive flexibility were assessed using an attentional set-shifting task (ASST) in order to investigate the effects of traumatic stress on cognitive flexibility. Additionally, the molecular alterations of certain proteins (AMPA Receptor 1 (GluA1), brain-derived neurotrophic factor (BDNF), and Postsynaptic density protein 95 (PSD95) in the medial prefrontal cortex (mPFC) were measured using Western blot and immunofluorescence. Results: The SPS&S model exhibited PTSD-like behaviors and induced reversal learning and set-shifting ability deficit in the ASST. These behavioral changes are accompanied by decreased GluA1, BDNF, and PSD95 protein expression in the mPFC. Further analysis showed a correlative relationship between the behavioral and molecular alterations. Conclusions: The SPS&S model induced cognitive flexibility deficits, and the potential underlying mechanism could be mediated by GluA1-related BDNF signaling in the mPFC.

Background Post-traumatic stress disorder (PTSD) is a debilitating mental disease with high morbidity and major social and economic relevance. No efficient treatment for PTSD has thus far been identified. Clinical research has shown that ketamine can rapidly alleviate symptoms in patients with chronic PTSD; however, its pharmacological mechanism has yet to be determined. Methods This study aimed to identify a model of single prolonged stress (SPS), which induced PTSD-like features in adult mice. Once the model was established, stress-related behavioral changes in the mouse model were evaluated after intraperitoneal injection of ketamine (10 mg/kg). Alterations in certain proteins (HCN1, BDNF, and PSD95) and synaptic ultrastructure in the prefrontal cortex (PFC) and hippocampus (HIP) were measured. Results The mice under the SPS model exhibited anxiety- and depression-like behaviors and induced spatial cognitive deficits, accompanied by elevated HCN1 protein expression in the PFC and HIP, reduced brain-derived neurotrophic factor (BDNF) and PSD95 proteins, and alterations in synaptic morphology. After ketamine administration, the SPS-treated mice restored their protein levels and synaptic ultrastructure in the PFC, and their PTSD-like behaviors improved. However, learning and memory in the SPS-treated mice did not improve in the water maze test, and no significant changes in protein level and synaptic ultrastructure in the HIP were shown. Limitations The electrophysiological mechanism of the HCN1 ion channel after ketamine administration was not explored. Conclusion Ketamine could generally improve SPS-induced mood dysfunction in mice but exerted no effect on the spatial cognitive function, which could be related to the alterations in synaptic morphology and function mediated by HCN1-related BDNF signaling in the PFC and HIP.

Objectives Alcohol dependence causes extensive damage to the central nervous system, resulting in impaired brain structure and behavioral changes. Moreover, histone deacetylase (HDAC) inhibitors restrain the activity of HDAC and cause increased histone acetylation, which may be related to alcohol dependence. Methods Ethanol dependence was modelled in animals by persistent alcohol exposure and tested in the conditioned place preference (CPP) paradigm. To induce CPP, the alcohol-treated rats were given orally gradient concentration (3%, 6%, and 9% v/v) alcohol administration for 20 consecutive days. The sodium butyrate (NaB)-treated rats were injected daily. Cognitive flexibility was evaluated using an attentional set-shifting task (ASST) in which the rats performed a series of seven consecutive discriminations after the final CPP paradigm. Results Ethanol administration induced alcohol dependence behaviors, with more time spent in the ethanol-paired compartment. Compared with the CPP scores of the control group, the scores of the ethanol- and NaB-treated groups were significantly higher. In the ASST, alcohol-treated rats had significantly increased number of trials to reach criteria (TTC) in most phases, higher error rate, and lower cognitive levels compared to the control group. Moreover, the present findings demonstrated that NaB combined with ethanol caused cognitive deficits as the result of an increased number of TTC during the ASST. Conclusions The attentional/cognitive flexibility of the prefrontal cortex of alcohol-dependent rats was damaged and the NaB administration procedure itself did not produce cognitive deficits, but instead exacerbated cognitive impairment in alcohol-dependent rats.

Computational lithography (CL) has become an indispensable technology to improve imaging resolution and fidelity of deep sub-wavelength lithography. The state-of-the-art CL approaches are capable of optimizing pixel-based mask patterns to effectively improve the degrees of optimization freedom. However, as the growth of data volume of photomask layouts, computational complexity has become a challenging problem that prohibits the applications of advanced CL algorithms. In the past, a number of innovative methods have been developed to improve the computational efficiency of CL algorithms, such as machine learning and deep learning methods. Based on the brief introduction of optical lithography, this paper reviews some recent advances of fast CL approaches based on deep learning. At the end, this paper briefly discusses some potential developments in future work.

Maternal separation (MS) causes long-lasting epigenetic changes in the brain and increases vulnerability to traumatic events in adulthood. Of interest, there may be sex-specific differences in these epigenetic changes. In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF were measured to determine whether BDNF influences risk of PTSD following MS in early life. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2~PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). In animals stressed with the SPS procedure in adulthood, those that had increased MS intensity in childhood demonstrated more significant changes in performance on tests of anxiety, depression, and contextual fear memory. Reduced levels of total BDNF mRNA and protein were observed after SPS treatment and further declined in groups with greater MS time in childhood. Interestingly, these changes were correlated with decreased H3K9ac levels and increased HDAC2 levels. Additional MS also led to more severe ultrastructural synaptic damage in rats that experienced the SPS procedure, particularly in the CA1 and CA3 region of the HIP, reflecting impaired synaptic plasticity in these regions. Interestingly, male rats in the MS3h-PTSD group showed decreased anxiety, but no similar changes were found in female rats, suggesting a degree of gender specificity in coping with stress after mild MS. In summary, this study suggests that the epigenetic signatures of the BDNF genes can be linked to HIP responses to stress, providing insights that may be relevant for people at risk of stress-related psychopathologies.

Barbula fallax Hedw., Erythrodontium julaceum (Schwaegr.) Par., and Bryum argenteum Hedw. are typical rock mosses growing on rocks in different terrestrial habitats. In this study, B. fallax and E. julaceum, which are epilithic mosses growing in rock desertification in Guizhou, China, were used as ecophysiological mosses in a combination of field investigations and laboratory experiments. We also investigated the reference moss B. argenteum, which is a widely distributed moss in habitats with soil as substrate. Our research focused on the response of the antioxidant defense system of epilithic mosses to drought stress. Most antioxidant defense indicators increased initially, then declined at later stages of drought stress. In contrast, the carotenoid content increased constantly. In addition, there was an initial increase (albeit variable) in relative membrane permeability, with this parameter showing a parabolic trend in all of the epilithic mosses. Among the three species, E. julaceum demonstrated the strongest resistance followed by B. fallax and then by B. argenteum. The epilithic mosses displayed stronger resistance compared to the native mosses; the increase in O 2 -· content and other reactive oxygen species (ROS) at the early stage of drought stress induced the enzymatic and non-enzymatic scavenging systems to sequester ROS. Moreover, the radical scavenging ability and strong drought tolerance was maintained. The long-term growth of bryophyte under drought conditions in a karst environment can help eliminate the intense response of mosses to drought stress as they adapt.

Forest vertical structure has significant influences on a series of structural and functional properties of forest ecosystems, and is often manipulated by silvicultural practices. However, how forest structure changes with stand height has not been well understood although their occurrence is highly correlated with forest management. An across-stand analysis of forest structure was conducted to characterize the structure of different stand heights in a Masson Pine plantation in southern subtropical China. Totally 238 plots were measured. We categorized all tree individuals into four layers according to tree height: the regeneration, lower, middle and upper layers. Species composition, species richness, abundance, diversity, DBH, volume, and slenderness were quantified and compared among four different stand layers. The results showed that (1) species richness and abundance index increased firstly and then decreased with increasing stand layer. (2) Tree individuals with diameter >20 cm dominated at the upper stand layer (tree height >15.6 m). (3) Although tree individuals at the lower layer contributed substantially to forest area at both plot and stand levels, their volume was less influential than larger trees because about 12.6% of the total tree individuals at the upper layer provided 46.5% of total volume. (4) Trees with stem slenderness values smaller than 100 and DBH >20 cm were predominantly located at the upper layer. The findings suggest that the features of vertical structure were useful for designing silvicultural systems of Masson pine plantation. Future research is needed to gain a better management strategy linked with structure characteristics.

Supplemental material for Effects of Close-to-Nature Conversion on Pinus massoniana Plantations at Different Stand Developmental Stages by Xiaoming Wang, Yuanchang Lu, Haitao Xing, Ji Zeng, Yangsheng Xie, Daoxiong Cai, Xianzhao Liu and Xianqiang Zhang in Tropical Conservation Science

Several long non-coding RNAs (lncRNAs) have been investigated and found to be correlated with the behaviours and prognosis of hepatocellular carcinoma (HCC); Specifically, we revealed that the lncRNA UC001kfo was differentially expressed in HCC tissues compared with normal liver tissues using lncRNA microarrays, but its functional role in cancers, including HCC, has not yet been elucidated. The present study found that the expression of UC001kfo was upregulated in HCC tissues and cell lines in comparison with tumour-adjacent tissues and normal hepatocytes, respectively. In addition, a high UC001kfo level was determined to be correlated with macro-vascular invasion and TNM stage of HCC. Specifically, patients with high UC001kfo expression displayed a significantly lower overall survival rate and progression-free survival rate. Moreover, both univariate and multivariate COX regression analyses identified TNM stage and high UC001kfo expression as risk factors for poor prognosis in HCC patients. In addition, UC001kfo was verified to promote the proliferation, metastasis and epithelial-mesenchymal transition (EMT) in HCC cells in both in vitro and in vivo assays. Mechanistically, α-SMA was indicated as a potential target gene of UC001kfo in mediating HCC metastasis. In conclusion, UC001kfo promotes HCC proliferation and metastasis by targeting α-SMA, and UC001kfo may potentially serve as a prognostic marker and a therapeutic target for treatment of HCC.

This paper presents several new control methods different from the classical PID control and modern control theory. Those control methods are simple without using the state equation of system and internal model principle, but its tracking performance is even better. Among those new controls, The ST-ER control and ST-ER-DE control are designed to control different kinds of precise linear systems to yield high tracking speed and low overshoot. GAST-ER control and GAST-ER-DE control respectively, base on ST-ER control and ST-ER-DE control are robust control methods which can track different kinds linear systems or approach linear systems with high tracking speed and almost no overshoot even when there is little or no information available regarding plant dynamics. In this paper, some simulation examples are given to demonstrate the effectiveness of those controls. Besides, The GAST-ER-DE control is applied to the micromirror plant without knowing its model and the experiment results are successful. With the new outlook and possibilities that GAST-ER control and GAST-ERDE control will promote a revolution in controlling field and break the hold of classical PID and enter a new era for its simplicity and high efficiency.

We consider implicit and semi-implicit time-stepping methods for continuous interior penalty (CIP) finite element approximations of Sobolev equations with convection-dominated term. Stability is obtained by adding an interior penalty term giving L2 -control of the jump of the gradient over element faces. Several -stable time-stepping methods are analyzed and shown to be unconditionally stable and optimally convergent. We show that the contribution from the gradient jumps leading to an extended matrix pattern may be extrapolated from previous time steps, and hence handled explicitly without loss of stability and accuracy. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2012

This study surveyed and analyzed the vegetation heterogeneity in the Center of Inner Mongolia (CIM) by a new method based on the beta-binomial distribution for each kind of vegetation. As many as 190 large quadrats of 5 mm × 5 mm (representing an area of 50 km × 50 km) (referred to as L-quadrats hereafter) were extracted from about an area of 475,000 km 2 . Each L-quadrat was divided into four small quadrats (S-quadrat) of 2.5 mm × 2.5 mm (equivalent to 25 km × 25 km) and the frequency of occurrence of each type of vegetation was recorded in each small quadrate. The weighted average heterogeneity from all of the vegetations composing a landscape provides a measure at landscape level to determine the spatial intricateness of landscape composition. Our results indicated that each vegetation has its own distribution pattern and the degree of heterogeneity is different from one kind of vegetation to the other. The results proved that the beta-binomial distribution can be very useful for analyzing vegetation landscapes.

The paper tests Hotelling's prediction that scarcity rent for a non-renewable resource will rise at the rate of discount in a market equilibrium. We perform the test using data for old-growth timber, a resource that is effectively non-renewable. In contrast to previous studies, for this resource a measure of scarcity rent is directly observable in the form of stumpage price bids in timber auctions. We construct a model that allows for replanting and captures the institutional framework of the western U.S. timber market. The modified Hotelling rule that we derive is not rejected in several of our specifications.

Close-to-nature (CTN) forestry integrates multiple forest functions and emphasizes forest ecosystem conservation. Within this framework, forests are typically maintained as uneven-aged mixed stands...

The main purpose of this paper is to make table tennis robots complete the hit table tennis ball action by imitating human's behavior. The main strategy is to record a video of action which people played the table tennis, then analysis the video of the racket trajectory. The racket in the image is extracted by image processing when the each frame is captured in the video. Then three-dimensional coordinates of the center of the racket and racket posture are obtained via PnP positioning approach based on the intrinsic parameters of the camera. The table tennis robot will off-line learn to complete the imitation of basic actions of the racket trajectory and postures. A large number of experimental data is used to establish basic actions of table tennis robot.

To establish the induction method and culture system of hairy roots of Panax japonicus, and determine ginsenoside Re contents.Hairy roots of P. japonicus was obtained through infecting pre-incubated terrestrial stem with the Agrobacterium tumefaciens strain C58C1; its enlarging culture was carried out on the 1/2MS medium, and growing characteristics were measured. The transformation of T-DNA was examined by PCR and ginsenoside Re content was determined by HPLC.A. tumefaciens strain C58C1 could make terrestrial stem of P. japonicus bring about hairy roots, the max inductivity was 90% when infecting for 25 min. The PCR examination result showed that rolB genes could be inserted into the hair roots of P. japonicus. All hairy roots dould synthesize ginsenoside Re, among them, the max content was PJ8 with 60. 26 mg x g(-1).It was reported for the first time that the induction method and culture system of hairy roots of P. japonicus were established successfully, which provided a foundation for producing high content ginsenoside Re through culturing the hairy roots of P. japonicus.