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Background: The prevalence of major depressive disorder in patients with schizophrenia (SZ-MDD) has been reported to be about 32.6 %, but it varies considerably depending on the stage (early or chronic) and state (acute or post-psychotic) of schizophrenia. The exploration of ideal strategies for the treatment of major depressive disorder in the context of schizophrenia is urgently needed. Thus, the present study was conducted to investigate the treatment effects of clozapine, electrical stimulation (ECS; the mouse model equivalent of electroconvulsive therapy for humans), venlafaxine, and mirtazapine for SZ-MDD.Methods: A mouse model of SZ-MDD was established with MK801 administration and chronic unpredictable mild stress exposure. Clozapine and ECS, alone and with mirtazapine and/or venlafaxine, were used as treatment strategies. In-vivo two-photon imaging was performed to visualize Ca2+ neural activity in the prefrontal cortex (PFC). Mouse performance on behavioral assays was taken to reflect acute treatment effects.Results: ECS + venlafaxine + mirtazapine performed significantly better than other treatments in alleviating major depressive disorder, as reflected by PFC Ca2+ activity and behavioral assay performance. Clozapine + venlafaxine + mirtazapine did not have an ideal treatment effect. Brain Ca2+ activity alterations did not correlate with behavioral expression in any treatment group.Conclusions: In this mouse model of SZ-MDD, ECS + venlafaxine + mirtazapine improved brain Ca2+ activity, pre-pulse inhibition, and immobility time. These findings provide useful information for the further exploration of treatment methods for patients with SZ-MDD, although the mechanisms underlying this comorbidity needed to be investigated further. [ABSTRACT FROM AUTHOR]

To explore the levels and predictors of body image dissatisfaction among women at different stages of pregnancy. This was a cross-sectional study design. A total of 863 Chinese pregnant women were recruited from a tertiary hospital via a convenience sampling method. Eligible participants completed a demographic questionnaire and self-reported measures of body image dissatisfaction, pregnancy-related anxiety, prenatal depression, and appearance comparison. Results showed no statistical difference in body image dissatisfaction levels among early-mid pregnancy (47.6 ± 6.17), late-mid pregnancy (47.3 ± 7.56), and late pregnancy stages (48.4 ± 6.22). The generalized linear model showed that gestational weight gain, pregnancy-related anxiety, own/family's perception of pregnancy weight, and current ideal weight change were predictors of body image dissatisfaction in the early-mid pregnancy stage. In addition, pre-pregnancy BMI, appearance comparison, own /family's perception of pregnancy weight, current ideal weight change, and overeating during pregnancy significantly predicted body image dissatisfaction in the late-mid pregnancy stage. Predictors of body image dissatisfaction in the late pregnancy stage comprised planned pregnancy, pre-pregnancy eating disorders, own perception of pregnancy weight, current ideal weight change, pregnancy-related anxiety, and prenatal depression. The findings suggest that predictors of body image dissatisfaction differed according to pregnancy stage. Self-perception of pregnancy weight was primary predictor of body image dissatisfaction. Healthcare professionals are recommended to provide prenatal health education to reduce own/family's negative perception of pregnancy weight, so as to alleviate the body image dissatisfaction level of pregnant women. [ABSTRACT FROM AUTHOR]

• eDNA metabarcoding demonstrated effective monitoring of freshwater snail biodiversity. • Environmental DNA methods can be used for early detection of invasive species. • eDNA technology could be applied to assess the ecological risk situation in lakes. Freshwater snails are a crucial benthic animal group that plays a pivotal role in algae regulation and ecosystems while serving as intermediate hosts for certain parasites. Environmental DNA (eDNA) technology offers numerous advantages for biodiversity assessment. However, the utilization of eDNA techniques for freshwater snail monitoring remains limited. In this study, we screened primers for assessing freshwater snail diversity using eDNA technology and constructed a comprehensive database for Poyang Lake. Using eDNA technology, a total of 21 species of snails were detected in Poyang Lake, while traditional methods detected only 11 species. Notably, all species collected by traditional methods were also detected by eDNA technology. Additionally, environmental DNA methods detected the invasive snail Pomacea canaliculata , while traditional methods did not. In this study, eleven intermediate host snail species for parasitic disease were identified using eDNA methods, while six were detected through traditional sampling techniques. The eDNA metabarcoding analysis showed that the α and β diversity levels of snails in Poyang Lake did not vary significantly, indicating that results obtained by eDNA sampling are not influenced by the season in which samples were collected. The correlation analysis between the community structure of snails and environmental factors in Poyang Lake revealed significant impacts of total nitrogen, chlorophyll a , water depth, and water temperature on the snail community structure. These results confirm that eDNA technology can be exploited to monitor freshwater snail biodiversity. [ABSTRACT FROM AUTHOR]

• This paper proposed a new method, DuFF-Net, for GPL classification from RGB and hyperspectral dual-modality images. • Presented an S-SimSiam self-supervised pre-training module to utilize the spectral and spatial features of HSIs. • Customized a dual-stream ResNet-based model to achieve information complementarity. • Increased the screening accuracy to 96.15 % while saving approximately 50 % labeling workload for classification tasks. Gastric precancerous conditions are closely linked to the development of gastric cancer. However, the detection of gastric precancerous lesions (GPL) is limited by the indistinct symptoms and the low detection rate of microscope images. This paper proposes an RGB and Hyperspectral Dual-modality imaging Feature Fusion Network (DuFF-Net) to improve the classification accuracy of GPL. To fully exploit information of different modality images, we customize a dual-stream ResNet-based model for feature sharing and fusion. Skip-Connections are added between inter-path of networks to achieve information interaction. In the decision step, we adopt the SE-based attention module and Pearson Correlation to highlight and select effective features. Experimental results show that the DuFF-Net increases the screening accuracy to 96.15 % for two types of gastric precancerous tissues with high morphological similarity. Furthermore, our approach reduces the labeling workload for classification tasks by approximately 50 %. These findings provide valuable guidance for the screening and subsequent lesion segmentation of GPLs. [ABSTRACT FROM AUTHOR]

• Visual hallucinations (VHs) had specific brain impairments. • Auditory hallucinations (AHs) had specific brain impairments. • Concurrent AHs and VHs showed severe brain and cognitive impairments. • VHs and AHs were reciprocally deteriorated in schizophrenia. • Strategies to block this reciprocal deterioration should be explored. Schizophrenic patients often experience visual hallucinations (VHs) and auditory hallucinations (AHs); however, brain aberrations associated with combined VH and AH in schizophrenic patients remains poorly documented. Changes to the brain and cognition during the first episode of untreated schizophrenic patients (FUSCH) with both VHs and AHs (FUSCHVA) were evaluated. One-hundred and fifty-seven patients were enrolled that had FUSCH (1) with VHs but not AHs (FUSCHV), and (2) with AHs but not VHs (FUSCHA), plus FUSCHVA and healthy controls (n = 30). Gray matter volume (GMV) and MATRICS Consensus Cognitive Battery (MCCB) was measured to reflect impairments to the brain and cognition, respectively. FUSCHVA patients had the severest cognitive impairment for all components of the MCCB, followed by FUSCHV and FUSCHA patients. Compared to healthy patients, FUSCHVA patients had reduced GMV in the occipital, parietal, frontal, and temporal cortex, and increased GMV in the hippocampus and striatum. Compared to FUSCHV patients, FUSCHVA patients had reduced GMV in the occipital cortex and postcentral gyrus, and increased GMV in the posterio-parietal lobe. Compared to patients with FUSCHA, the GMV in patients with FUSCHVV was reduced in the occipital cortex and posterio parietal lobe. In conclusion, visual and auditory hallucinations appear to deteriorate reciprocally in FUSCHVA patients, accompanied with sever cognitive impairments. Compared to AHs, VHs might be accompanied with severe GMV impairment in the brain, especially in the primary visual cortex and higher perception integration cortex (posterio parietal lobe) in patients with FUSCH. [ABSTRACT FROM AUTHOR]

We present the generation of optofluidic lasers in a Fabry-Pérot (FP) microcavity with low pumping threshold. The FP microcavity is constructed with one micro-concave mirror and another planar mirror facing each other to form a stable cavity. The two mirrors are coated with dielectric layers with reflectivity ≥99.9%. Laser behaviors are tested with gain medium, Rhodamine 6 G (R6G), dissolved in ethanol and ion water, respectively; a lowest pumping threshold as small as 0.13 μJ/mm 2 is achieved in the ethanol solution, corresponding to a theoretically calculated quality value Q 0 about 4×10 5 . Meanwhile experimental results demonstrates that the lowest concentration of dye medium that can emit laser signal in the FP microcavity is 3 μM. [ABSTRACT FROM AUTHOR]

• Ascaris lumbricoides and A. suum were examined for cross-infection and hybridization. • Hybrid identification by the two methods was inconsistent. • Microsatellite markers can be used for more reliable identification of hybrids. • Hybrid Ascaris were found to infected pigs in Xinjian County, Jiangxi Province. The discovery of hybrids between Ascaris lumbricoides and Ascaris suum has complicated our understanding of the relationship between the two species. We examined the same Ascaris specimens (48 from humans and 48 from pigs) using two methods: microsatellite markers combined with Bayesian clustering and PCR-RFLP of the nuclear internal transcribed spacer region. The results obtained by the two methods were inconsistent but showed that hybrid Ascaris identified through both approaches could infect pigs. The results of this study suggest that PCR-RFLP of ITS alone is not suitable for molecular identification of human-type and pig-type Ascaris hybrids. Use of multiple SSR markers combined with Bayesian analysis was the most reliable method in our study. Our results indicate that, in addition to host-specific Ascaris types, there may be some that do not show host specificity. Our results show for the first time that hybrid individuals can infect pigs as well as humans. This study has important theoretical and practical implications, including suggesting the need to re-evaluate long-term ascariasis control strategies. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study is to detect the frequency and distribution of cross infection and hybridization of human and pig Ascaris in China. Twenty high polymorphic microsatellite loci were selected to screen 258 Ascaris worms from humans and pigs from six provinces in China. The software programs Structure, Baps and Newhybrids were used to determine the case of cross infection and hybridization of human and pig Ascaris. Results showed that cross infection was detected in all sampled locations and of the total 20 cross infection cases, 19 were indentified as human infections by pure-bred pig type Ascaris in contrast to only one case of pig infection by pure-bred human type Ascaris. Similar to the findings in cross infection, hybrid Ascaris was also detected in all locations and both host species and most of hybrids (95%) were detected from human host. The distribution of cross infection and hybrids showed significant difference between the two host species and among three categories of genotype in terms of G1, G2 and G3, and also between the south and north regions (for hybrids only). The results strongly suggest pig Ascaris as an important source of human ascariasis in endemic area where both human and pig Ascaris exist. In consideration of current control measures for human ascariasis targeting only infected people, it is urgently needed to revise current control measures by adding a simultaneous treatment to infected pigs in the sympatric endemics. The knowledge on cross transmission and hybridization between human and pig Ascaris is important not only for public health, but also for the understanding of genetic evolution, taxonomy and molecular epidemiology of Ascaris. [Copyright &y& Elsevier]

[Display omitted] • MnO 2 /IrO 2 was one-step synthesized and possesses the excellent viability. • The MnO 2 affords the MR imaging and triggers the decomposition of H 2 O 2. • The in-situ formed O 2 promotes the production of cancer cell-toxic 1O 2. • The in-situ formed 1O 2 enhances the tumor photodynamic therapy efficiency. In this research, MnO 2 /IrO 2 nanoplatform was one-step synthesized from the heat-induced oxidation-reduction between potassium permanganate and iridium chloride and modified with polyvinylpyrrolidone (PVP) on the surface to obtain MnO 2 /IrO 2 -PVP nanoparticles (MIP NPs) with excellent colloidal stability of biocompatibility. Then, the photosensitizer Chlorin e6 (Ce6) was loaded onto the surface of MIP NPs. The IrO 2 can efficiently transform the 808 nm near-infrared laser into heat with a photothermal conversion of 27.57 % for tumor photothermal therapy. Interestingly, the MnO 2 can not only react with the redundant H+ and realize the magnetic resonance imaging of the tumor but also catalytic the decomposition of H 2 O 2 in the tumor to generate O 2 and relieve the hypoxia status of the tumor. The in-situ formed O 2 can promote the production of cancer cell-toxic singlet oxygens (1O 2) under the irradiation of 660 nm laser and boost the tumor photodynamic therapy efficiency. Moreover, it was found that PVP can fall off from the MIP NPs to increase their accumulation in the tumor. Such a MIP/Ce6-based nanoplatform which plays the synergism with tumor microenvironment shows promising potential for the combined photo-therapy of the tumor. [ABSTRACT FROM AUTHOR]

Human colorectal cancer (CRC) is treated with 5-fluorouracil (5-Fu). However, this drug causes various adverse effects, suggesting the benefit of developing safer natural-based drugs with high specificity and tolerable adverse effects. Dendrobium officinale has been used as a functional food and important medicine in China for more than a thousand years. The natural polysaccharides obtained from D. officinale (DOPW-1) show inhibitory activity against cancer cells. This study aimed to comparatively investigate the anticancer activity of DOPW-1 and mannose (Mann) on HT-29 cells and explored the possible underlying molecular mechanisms of CRC treatment. HT-29 cells were treated with 5-Fu, DOPW-1, and Mann or their combinations. Cell viability and apoptosis were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Hoechst 33342 with annexin V-fluorescein isothiocyanate/propidium iodide assays, respectively. DOPW-1 showed good antitumor effects on HT-29 cells and significantly potentiated the anticancer activities of 5-Fu in vitro and in vivo. DOPW-1 significantly inhibited tumor metastasis in the zebrafish model. Furthermore, the monosaccharide composition of DOPW-1 might not have an important effect on its antitumor activity. The results of Western blot analysis suggested that DOPW-1 alone and in combination with 5-Fu induced cell apoptosis using the mitochondria-dependent intrinsic apoptotic pathway. Thus, DOPW-1 is a potential source of natural polysaccharides for CRC therapy alone or in combination with 5-Fu. [Display omitted] • Dendrobium officinale polysaccharide (DOPW-1) showed good antitumor effects. • DOPW-1 significantly potentiated anticancer effects of 5-Fu in vitro and in vivo. • DOPW-1 significantly inhibited tumour metastasis in the zebrafish model. • Mannose content of DOPW-1 did not mediate antitumor activity against CRC. • DOPW-1 induced apoptosis in CRC using the mitochondria-dependent apoptotic pathway. [ABSTRACT FROM AUTHOR]

Atomically-thin Janus heterojunctions exhibit extraordinary electronic and optoelectronic properties, mainly due to their intrinsic built-in electric field. However, current investigations are limited within layered metal chalcogenides. Here, a free-standing ultra-thin Janus metal oxychalcogenide is realized from non-layered In 2 S 3. In the presence of strong mechanical agitation in the liquid medium, the original tetragonal crystal is cleaved. Ambient oxygen atoms are subsequently diffused and incorporated into limited part of the crystal structure, forming the oxysulfide phase with the gradual transition into a hexagonal structure. While the integrity of the covalent bonding system is maintained, a tensile strain is generated as a result of the crystal coordination mismatching between the pure sulfide and oxysulfide phases, leading to a more than two orders enhancement on visible-light-driven exciton lifetime compared to that of pure In 2 S 3. Such an impressive excitonic interaction provides the fundamentals to establish an ultra-sensitive and power-saving optoelectronic chemical sensing platform. As an example, dipoles generated by the surface adsorbed NO 2 molecules cause significant re-distribution of photoinduced charges in the anisotropic non-layered Janus structure under visible light low-power excitation, resulting in a superior sub-ppb detection limit of NO 2 gas at room temperature. [Display omitted] • Free-standing Janus indium oxysulfide is formed from In 2 S 3 with oxygen incorporation. • Surface crystal transfer is due to the replacement of sulfur by diffused oxygen. • Deteriorated exciton binding energy and recombination rate; prolonged PL lifetime. • Visible-light-driven gas sensor is ultrasensitive to NO 2 gas at room temperature. • The limit of detection (LOD) is in parts-per-trillion (ppt) range. [ABSTRACT FROM AUTHOR]

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents significant challenges to midwives and nurses. This study aimed to explore midwifery and nursing interventions to limit the transmission of COVID-19 among women in their third trimester of pregnancy, to reduce the incidence of nosocomial infection and promote safety of care for women and their infants. We completed a retrospective review of medical records from 35 women in their third trimester of pregnancy with SARS-CoV-2, admitted to one hospital in Wuhan, China in January and February 2020. We investigated the clinical characteristics of the COVID-19 infection in pregnancy, and the individualized midwifery and nursing care offered, including environmental protection, prevention of nosocomial infection, maternal observations, monitoring of signs and symptoms of COVID-19, and psychological care. Thirty-one women had a caesarean section, and four had vaginal births. Retrospective analysis of midwifery and nursing strategies implemented to care for these women showed no maternal complications or nosocomial infections. The care strategies we implemented could prevent complications and nosocomial infection in the third trimester of pregnancy, thus ensuring the safety of women and their infants. Further research needs to determine treatment priorities for women infected with COVID-19 during pregnancy and the postnatal period. [ABSTRACT FROM AUTHOR]

• The mitochondrial genomes of three Ascaris populations were sequenced. • The Ascaris populations sequenced in this study were all gathered in cluster B. • The human-type and hybrid Ascaris populations belonged to different sub-clusters. • Ascaris populations were geographically isolated before host shift in China. Ascaris lumbricoides and Ascaris suum are parasitic nematodes in human and pig intestines. The two species can cross infect and produce hybrids, which contribute to the controversy concerning the taxonomy of A. lumbricoides and A. suum. The purpose of this study was to investigate the microevolutionary process and evolutionary history of human-type Ascaris, pig-type Ascaris, and hybrid Ascaris and provide a theoretical basis for the prevention and control of human and animal ascariasis. The mitochondrial phylogenomics of human-type Ascaris (n = 5), pig-type Ascaris (n = 6), and hybrid Ascaris (n = 6) populations were analyzed using high-throughput sequencing technology. The mitochondrial genomes of human-type Ascaris , pig-type Ascaris , and hybrid Ascaris contained 36 genes (atp 8 was missing), including 12 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. All genes were located on the heavy chain. The initiation codons used for protein-coding genes were ATT and TTG and the termination codons were TAA and TAG. The base distribution showed obvious AT preference. The phylogenetic tree based on the Ascaris mitochondrial genomes showed three main clusters (A, B, and C). The Ascaris populations sequenced in this study were all gathered in cluster B. The human-type and hybrid Ascaris populations belonged to different sub-clusters, but the pig-type Ascaris population was more scattered. The mitochondrial genome sequences of the 17 Ascaris individuals in this study did not differ much. The results of this study indicate that Ascaris populations were geographically isolated before host shift. In addition, the data show that there are differences between hybrid Ascaris, human-type Ascaris, and pig-type Ascaris. The information has important theoretical significance and application value. [ABSTRACT FROM AUTHOR]

• The whole genomes of two Ascaris populations were resequenced. • The A. lumbricoides population was more primitive than the A. suum population. • Two KEGG pathways but no GO terms were enriched in the A. lumbricoides population. • Five GO entries and one KEGG pathway were enriched in the A. suum population. • Ascaris population sizes peaked about 1 million years ago and then declined. Ascaris lumbricoides and Ascaris suum are parasitic nematodes that mainly parasitize the small intestines of people and pigs, respectively. Ascariasis seriously endangers human health and causes huge economic losses in the pig industry. A. lumbricoides and A. suum have similar morphologies and genetic structures, and occasionally these organisms cross-infect the alternate host. Therefore, their taxonomies are controversial. In this study, the whole genomes of A. lumbricoides (n = 6) and A. suum (n = 6) were resequenced using a HiSeq X Ten sequencing platform. Phylogenetic, principal component, and population structure analyses showed clear genetic differentiation between the two Ascaris populations. Linkage disequilibrium analysis indicated that the A. lumbricoides population was more primitive than the A. suum population. In the selective elimination analysis, 160 and 139 candidate regions were screened in A. lumbricoides and A. suum , respectively, and the selected regions were analyzed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The A. lumbricoides population had no significant enrichment in GO terms, but two KEGG pathways, the RNA degradation and tyrosine metabolism pathways, were significantly enriched. Five GO entries and one KEGG pathway, the alanine, aspartate, and glutamate metabolism signaling pathway, were significantly enriched in the A. suum population. An analysis of the demographic histories of Ascaris populations revealed that A. lumbricoides and A. suum had similar trends in effective population size in different historical periods. Ascaris populations peaked about 1 million years ago and then began to decline. In the last glacial period, they dropped to a historical low and continued at this level until the last glacial maximum. This phenomenon may be associated with the cold climate at that time. This study provides new information on the genetic differentiation, evolutionary relationships, gene functional enrichment, and population dynamics of Ascaris populations, with implications for host differences, evolution, and classification of A. lumbricoides and A. suum. [ABSTRACT FROM AUTHOR]

Auditory verbal hallucination (AVH), defined as the auditory perception of speech in the absence of a real external stimulus, occurs in individuals with and without mental illness. The distribution of functional abnormalities in patients with AVH suggests aberrant brain network connectivity. However, no study has measured the global functional connectivity density (gFCD) associated with AVH in patients with major depressive disorder (MDD); gFCD is used widely to examine the density distribution of whole-brain resting-state functional connectivity and can serve as an index reflecting brain metabolism disturbance. In this study, we involved drug-naïve patients with first-episode MDD with (n = 35) and without (n = 40) AVH and healthy controls (n = 50).Whole-brain resting-state functional magnetic resonance imaging data were acquired and gFCD was calculated and compared among groups. We found the following gFCD alterations that were shared by both MDD groups: (1) decreased gFCD in the bilateral postcentral gyrus, precentral gyrus, insular cortices and occipital lobe; and (2) increased gFCD in the left middle cingulate cortex. More importantly, we found AVH-specific gFCD changes in patients with MDD: increased gFCD in the left Wernicke's brain regions and bilateral hippocampus and thalamus, and decreased gFCD in the bilateral lateral prefrontal lobule. These findings reflect the disturbance of brain information communication and metabolism in patients with MDD and AVH, related mainly to the language and memory processing circuits, and to some extent provide further support for the "VOICE" model of AVH. • Global functional connectivity density (gFCD) was calculated to investigate brain density distribution of whole-brain resting-state functional connectivity and can serve as an index reflecting brain metabolism disturbance. • We involved drug-naïve patients with first-episode MDD with and without AVH and healthy controls and gFCD was calculated and compared among groups. • Our findings reflect the disturbance of brain information communication and metabolism in patients with MDD and AVH, related mainly to the language and memory processing circuits. [ABSTRACT FROM AUTHOR]

In order to improve the wear resistance of titanium alloys, the Zr-based amorphous-nanocrystalline coatings were prepared by Electrospark Deposition (ESD) on the surface of TC11. The microstructure of the coatings was analyzed and the tribological behavior and mechanism of the coatings were investigated. The results show that the coating is mainly composed of amorphous phase Zr 55 Cu 30 Al 10 Ni 5 and distributed a large number of nano particles with the diameter between 2 nm and 4 nm such as CuZr 3 , Ni 2 Zr 3 , NiZr 2 , etc. The new alloy system made up of molten electrode material of Zr-based alloy and TC11 substrate has a large glass forming ability, which transforms to amorphous phase in the rapid heating and cooling ESD process. The long-range diffusions of atoms such as Zr and Cu in amorphous microstructure play an important role in nano nucleation growth. The coating is dense, uniform, bonding with TC11 substrate metallurgically. The thickness of the coating is from 55 μm to 60 μm and the average microhardness is 801.3 HV 0.025 . The coating has good friction-reducing and anti-wear properties. The friction coefficient of the coating changes between 0.13 and 0.21 with small fluctuation, decreasing about 60% compared to that of TC11 substrate. And the wear resistance of the coating is increased by 57% than that of TC11 substrate. The main wear mechanism of the coating is micro-cutting wear accompanied with oxidation wear. [ABSTRACT FROM AUTHOR]

TQ-B3139 is a novel ALK tyrosine kinase inhibitor (TKI) against a broad range of ALK mutations. The aim of this first-in-human phase I trial was to investigate the safety, tolerability, pharmacokinetics, and clinical efficacy of TQ-B3139 in ALK or ROS1 positive advanced NSCLC patients. Following a 3 + 3 design, patients received escalating daily dose of TQ-B3139 (50–800 mg) continuously in 28-day cycles. Expansion stage started at dose of 200 mg twice daily (BID). The primary objectives were the safety, dose-limited toxicities (DLT) and recommended phase II dose (RP2D); secondary objectives included pharmacokinetics and antitumor activity. Non-obligatory tumor samples at baseline were collected and sequenced. The study enrolled 63 patients. Fifty-nine (93.4%) patients experienced treatment-related adverse events (TRAEs), mostly grade 1–2 vomiting (79.3%), diarrhea (76.1%) or nausea (68.2%). 1 (1/6) DLT occurred at 600 mg BID and 1 (1/3) at 800 mg BID. Based on safety and pharmacokinetics data, the RP2D was selected as 600 mg BID. At a dose level ≥200 mg BID, the overall response rate (ORR) was 76.7% (33/43), and the median progression free survival (mPFS) was 25.2 months (95%CI 11.9-NR) for TKI-naive patients. For TKI-treated patients, the ORR was 37.5% (6/16), and the mPFS was 5.4 months (95%CI 3.6–9.1). The ORR was 66.7% (2/3) in patients with ROS1 fusion at dose level ≥200 mg BID. In patients with measurable brain metastases, the intracranial ORR was 70% (7/10), with median intracranial PFS of 15.9 months. In TKI-treated patients, variant 3 and TP53 alteration were associated with poor PFS. TQ-B3139 was well-tolerated and exhibited promising anti-tumor activities in patients with ALK and ROS1 positive advanced NSCLC. NCT03099330. • TQ-B3139 is a novel second generation ALK-TKI, also inhibiting ROS and c-Met. • TQ-B3139 has promising antitumor activity and tolerated toxicity. • Favorable intracranial ORR and PFS were observed in ALK + NSCLC patients. • Variant3 and TP53 alteration were associated with poor PFS in TKI-treated patients. [ABSTRACT FROM AUTHOR]

Abstract: Changes in cytokine and chemokine expression during Wallerian degeneration have been studied using nerve transection models, which result in denervation of both myelinating and non-myelinating Schwann cells. Cytokine and chemokine response of non-myelinating Remak Schwann cells to loss of their axons is unknown. In this study, we compared the expression profile of various cytokines and chemokines in distal nerves after capsaicin-induced degeneration of unmyelinated axons to Wallerian degeneration induced by nerve transection. Upregulation of MCP-1, IL-2, IL-6 and IL-10 were seen in both groups but IL-1ß and LIF were primarily upregulated in Wallerian degeneration of the whole nerve and not in capsaicin-induced degeneration of unmyelinated axons. The activated macrophage response, as measured by an increase in ED-1 immunostaining, was more prominent in the transected sciatic nerves compared to capsaicin-treated nerves. These findings indicate that there are differences in the cytokine and chemokine response of myelinating and non-myelinating Schwann cells to loss of their axons, and add to a growing body of literature that points to greater heterogeneity among Schwann cells. [Copyright &y& Elsevier]

Background: Two distinct subtypes of treatment-resistant schizophrenia (TRS) have been recently reported, including early-treatment resistance (E-TR) and late-treatment resistance (L-TR). This study was to assess clozapine-induced metformin-resistant prediabetes/diabetes and its correlation with clinical efficacy in schizophrenia E-TR subtype.Methods: This prospective cohort study enrolled 230 patients with schizophrenia E-TR subtype and they were treated with adequate doses of clozapine for 16 weeks, during which patients with prediabetes/diabetes were assigned to receive add-on metformin. The main outcomes and measures included incidence of clozapine-induced prediabetes/diabetes and metformin-resistant prediabetes/diabetes, and the efficacy of clozapine as assessed by the Positive and Negative Syndrome Scale (PANSS) score.Results: Clozapine-induced prediabetes/diabetes occurred in 76.52% of patients (170 prediabetes and 6 diabetes), of which the blood sugar of 43 (24.43%) patients was controlled with metformin. Despite add-on metformin, 47.06% (74/170) of prediabetes patients progressed to diabetes. In total, the incidence of clozapine-induced metformin-resistant prediabetes/diabetes was 75.57% (133/176). On completion of 16-week clozapine treatment, 16.52% (38/230) patients showed clinical improvement with PANSS scores of ≥50% declining. Furthermore, clozapine-induced prediabetes/diabetes was significantly correlated with the poor clinical efficacy of clozapine for schizophrenia E-TR subtype.Conclusions: The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in the schizophrenia E-TR subtype. Clozapine-induced metformin-resistant prediabetes/diabetes represents an independent risk factor that adversely affects the clinical efficacy of clozapine for the schizophrenia E-TR subtype. This study provided new evidence for re-evaluating the use of clozapine for TRS, especially E-TR subtype, and the use of metformin for the glycemic control of clozapine-induced prediabetes/diabetes. [ABSTRACT FROM AUTHOR]

Carboxymethyl cellulose derivatives bearing tetrabutylammonium moieties (CMC-TBA) were synthesized by the acidification of carboxymethyl cellulose (CMC) followed by acid-base neutralization with tetrabutylammonium hydroxide. The products were identified by Fourier transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR) spectroscopy and the degrees of substitution (DS) values were also quantified according to the integral area values in 1H NMR spectra. It was revealed that DS values had a positive relationship with the molar ratios of TBAOH to CMC. The antibacterial behaviors against gram-positive bacteria S. aureus and gram-negative bacteria E. coli were investigated using serial two-fold dilution method (MIC and MBC) and the disc diffusion method (inhibition zone). The results showed that comparison with CMC, all new CMC-TBA derivatives exhibited high antibacterial activity that depends on bacteria type and their degrees of cationization. The antibacterial action was more effective against S. aureus than E. coli , which could be attributed to the fact that the latter has a complicated bilayer structure of cell wall. Besides, an apparent tendency that the antibacterial activity of CMC-TBA derivatives enhanced with an increase in the degrees of cationization was found. This work suggests that these new derivatives can be introduced as efficient antibacterial biomaterials for biomedical purposes. • Carboxymethyl cellulose derivatives bearing tetrabutylammonium were synthesized. • DS values had a positive relationship with the molar ratios of TBAOH to CMC. • The novel derivatives exhibited high antibacterial activity compared with CMC. • Bacteria type and cationization degrees could affect the antibacterial activity. [ABSTRACT FROM AUTHOR]

Gastric precancerous lesions (GPL) significantly elevate the risk of gastric cancer, and precise diagnosis and timely intervention are critical for patient survival. Due to the elusive pathological features of precancerous lesions, the early detection rate is less than 10%, which hinders lesion localization and diagnosis. In this paper, we provide a GPL pathological dataset and propose a novel method for improving the segmentation accuracy on a limited-scale dataset, namely RGB and Hyperspectral dual-modal pathological image Cross-attention U-Net (CrossU-Net). Specifically, we present a self-supervised pre-training model for hyperspectral images to serve downstream segmentation tasks. Secondly, we design a dual-stream U-Net-based network to extract features from different modal images. To promote information exchange between spatial information in RGB images and spectral information in hyperspectral images, we customize the cross-attention mechanism between the two networks. Furthermore, we use an intermediate agent in this mechanism to improve computational efficiency. Finally, we add a distillation loss to align predicted results for both branches, improving network generalization. Experimental results show that our CrossU-Net achieves accuracy and Dice of 96.53% and 91.62%, respectively, for GPL lesion segmentation, providing a promising spectral research approach for the localization and subsequent quantitative analysis of pathological features in early diagnosis. • This paper presented a dual-modality CrossU-Net for lesion segmentation of gastric precancerous from RGB and HSI images. • Developed a Spectral-wise Siamese (SpeSiam) self-supervised pre-training module that focuses on spectral analysis. • Designed a dual-stream Cross-attention U-Net network to improve lesion tissue identification. • Demonstrated the effectiveness of our approach through comparisons with single-modal methods for pathological diagnosis. [ABSTRACT FROM AUTHOR]

• OTAVH are reported to be associated with brain alterations. • OTAVH showed unified and specific brain features among 6 mental disorders. • Psychometric scores did not correlate to the brain features. • The unified brain features may be uninfluenced by the diagnosis category. • The specific brain features may be influenced by the specific trait of the disease. To explore the unified and disease specific structural features of the brain in patients spanning six mental disorders who experience own-thought auditory verbal hallucinations (OTAVH). A pilot study was conducted on 25 patients with schizophrenia (FUSCH-OTAVH), 20 patients with major depression disorder (FUMDD-OTAVH), 28 patients with bipolar disorder (FUBD-OTAVH), 22 patients with posttraumatic stress disorder (FUPTSD-OTAVH), 21 patients with anxiety disorder (FUAD-OTAVH), and 27 patients with borderline personality disorder (FUBPD-OTAVH). Twenty-five healthy controls (HCs) were also recruited. Auditory Hallucinations Rating Scale (AHRS) multiple psychometric scales were adopted to assess the clinical features of voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and multiple regression in all patients. Common and specific brain features of OTAVH among these mental disorders were investigated. Compared to HCs, GMV aberrant pattern across all the six categories patients with OTAVH decreased in the occipital cortex, left parietal lobe, prefrontal cortex (PFC), and insular cortex (IC). Aberrant patterns in white matter (WM) were detected in the corpus callosum and impairment of the fronto-occipital fasciculus. Structural differences in the brain were observed for each mental disorder versus HCs. The unified brain aberrant features of OTAVH across six mental disorders were characterized by decreased GMV and WM impairments in some regions and the specific brain features of each disease were also characterized. In conclusion, this study provides evidence for the structural basis of OTAVH and potential avenues for investigating disease specific brain features of OTAVH. [ABSTRACT FROM AUTHOR]

• The first study to evaluate acquired resistance for 1st line EGFR-TKI plus Bevacizumab (A + T). • Mutation ratio of T790 M was decreased in A + T group compared with single T group. • SMAD4 mutations and EGFR p.V834 L were regarded as novel acquired resistance to A + T. • Real world data proves A + T significantly extends PFS with acceptable safety profile. We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor (TKI, T) plus bevacizumab (an antiangiogenic therapy, A) in a real-world population and to provide insights into their mechanism of resistance. This study included 256 NSCLC patients harboring EGFR sensitizing mutations (EGFR 19del and L858R) who underwent nextgeneration sequencing (NGS) with 168-gene panel prior to treatment between Jan 2015 to Aug 2018. Cohort A included 60 patients treated with A + T; while cohort B consisted of 120 patients treated with EGFR-TKI monotherapy with the patients identified using Propensity Score Matching (Ratio of 1:2). Clinical outcomes and potential resistance mechanism were evaluated. Baseline clinical characteristics were not significantly different between Cohort A and B. Compared with cohort B, cohort A had significantly better overall response rate (95% vs 74.2%, p = 0.001) and longer median progression-free survival (PFS, 16.5m vs.12.0 m, HR = 0.7, p = 0.001). Until Jan 2019, 31 and 103 patients in cohort A and B, respectively, were evaluated with progressive disease and underwent tissue re-biopsy and NGS profiling with 168-gene panel. In cohort B, T790M was the predominant acquired resistance mechanism, detected in 51.5% (53/103) of progressive tumors, followed by amplifications in EGFR (15.5%, 16/103) and MET (6.8%, 7/103). Contrastingly, cohort A had a significantly lower rate of T790 M mutation (35.5%, 11/31, p = 0.0003), followed by mutations in TP53 (29.0%, 9/31), RB1 (9.7%, 3/31), SMAD4 (3.2%, 1/31) and EGFR V834 L (3.2%, 1/31) and amplifications in EGFR (9.7%, 3/31), and MET (6.5%, 2/31). Treatment with first-line A + T significantly extends the time to progression and increases the response rate with acceptable safety profile. T790 M was the most common acquired resistance mechanism but it was less common in patients who received A + T. [ABSTRACT FROM AUTHOR]

Highlights • Auditory verbal hallucinations (AVHs) are severe symptoms of post traumatic distress disorder (PTSD). • AVHs is related to brain functional disturbances in the salience network(SN). • PTSD patients with AVHs benefit from atypical anti-psychotic treatment. • Atypical anti-psychotic treatment can decrease the functional activity of SN. • The decrease in functional connectivity within the SN was significantly correlated with the reduction in total AVHs assess scores. Abstract Auditory verbal hallucinations are common symptoms of post traumatic distress disorder. Previous studies have demonstrated alterations in the salience network (SN) in patients with post traumatic distress disorder and that hyperactivity of the SN is associated with AVHs in patients with psychosis. Patients with post traumatic distress disorder may benefit from aripiprazole; however, studies investigating the effect of aripiprazole on AVHs and activity in the SN in patients with post traumatic distress disorder are scarce. Therefore, we conducted an outcomes analysis using functional magnetic resonance imaging to explore the effects of add-on aripiprazole treatment on AVHs and brain functional connectivity in patients with post traumatic distress disorder. AVHs were alleviated by add-on aripiprazole treatment (Auditory Hallucination Rating Scale [AHRS] score reduced by ≥ 50%) in 22.7% of patients. Functional activity in the SN was obviously decreased in patients in whom AHRS scores were reduced ≥ 50% following add-on aripiprazole treatment compared to patients in whom AHRS scores were reduced by <50%. The decrease in functional connectivity within the SN was significantly correlated with the reduction in total AHRS scores. Although this study was associated with several limitations, the findings suggest that add-on aripiprazole treatment can alleviate AVHs in patients with post traumatic distress disorder by reducing activity in the SN. [ABSTRACT FROM AUTHOR]

In this study, a novel, effective and environment-friendly methods was used to prepare poly- l -lysine (PLL)-functionalized magnetic Fe 3 O 4 -(GO-MWCNTs) hybrid composite with large surface area and abundant hydroxyl and amino groups. The as-prepared PLL-Fe 3 O 4 -(GO-MWCNTs) nanocomposite was systematically characterized by FT-IR, XRD, TGA, SEM, TEM, VSM and EDX. The PLL-Fe 3 O 4 -(GO-MWCNTs) hybrid composite exhibited excellent adsorption performance for the removal of a dye (tartrazine) and a heave metal (Pb(II)). The result showed that adsorption of Pb(II) reached equilibrium in 30 min and adsorption of tartrazine reached equilibrium in approximately 60 min. Most importantly, PLL-Fe 3 O 4 -(GO-MWCNTs) hybrid possesses high adsorption capacity, rapid separation, and less time-consuming. The equilibrium adsorption capacity was 1038.42 mg g −1 for Pb(II) and 775.19 mg g −1 for tartrazine under the optimal conditions. These two pollutants removal were found to obey Langmuir adsorption model, while the kinetics of adsorption followed pseudo-second-order kinetic model. A possible adsorption mechanism has been proposed where the chelation between PLL and Pb(II) or electrostatic interaction between GO and tartrazine. These results demonstrated the potential applications of PLL-Fe 3 O 4 -(GO-MWCNTs) hybrid composite in deep-purification of polluted water. [ABSTRACT FROM AUTHOR]

A kind of double-layered self-assembly sodium alpha-olefin sulfonate (AOS) capped Fe 3 O 4 magnetic nanoparticles (Fe 3 O 4 -AOS-MN) with highly water-solubility was prepared by a wet co-precipitation method with a pH of 4.8. The resulting Fe 3 O 4 -AOS-MN could be dispersed into water to form stable magnetic fluid without other treatments. The result of X-ray diffraction (XRD) indicated that the Fe 3 O 4 -AOS-MN maintained original crystalline structure and exhibited a diameter of about 7.5 nm. The iron oxide phase of nanoparticles determined by Raman spectroscopy is Fe 3 O 4 . Transmission electron microscopy (TEM) analysis confirmed that the Fe 3 O 4 -AOS-MN with spherical morphology were uniformly dispersed in water. FT-IR spectroscopy (FT-IR) and thermo-gravimetric analysis (TGA) verified the successful preparation of Fe 3 O 4 -AOS-MN capped with double-layered self-assembled AOS. The corresponding capacities of monolayer chemical absorption and the second-layer self-assembly absorption were respectively 4.07 and 14.71 wt% of Fe 3 O 4 -MN, which were much lower than those of other surfactants. Vibrating sample magnetometer (VSM) test result showed Fe 3 O 4 -AOS-MN possessed superparamagnetic behavior with the saturation magnetization value of about 44.45 emu/g. The blocking temperature T B of Fe 3 O 4 -AOS-MN capped with double-layered AOS is 170 K. [ABSTRACT FROM AUTHOR]

WC and CeO2 particles reinforced in-situ synthesized NiAl matrix (WC/CeO2/NiAl) composite coatings were prepared on aluminum alloys by laser surface alloying. The microstructure, microhardness and fracture toughness as well as the tribological properties at 25°C and 400°C of the composite coatings were investigated. The results show that the WC/CeO2/NiAl composite coating contains the phases of NiAl, WC, W2C, γ-(Fe,Ni), CrB, Cr23C6, Al3Ni2 and CeNi5. Due to the synergistic strengthening effects of WC and CeO2 particles, the average grain size of the composite coating is reduced, and the microhardness and fracture toughness are increased. The friction coefficient and wear loss of the composite coatings rise in ascending order with the temperature, which are smaller than those of the WC/NiAl composite coatings, the NiAl coatings and the substrates. As the temperature increases from 25°C to 400°C, the wear mechanisms of the composite coatings change from micro-cutting wear into multi-plastic deformation wear and slight oxidative wear. [ABSTRACT FROM AUTHOR]

Two soil samples were collected at mining areas located in southern Hunan Province, China. EDTA extraction of Pb, Zn, Cu and Cd from these two tailing soils was studied using column leaching experiments. The redistributions of heavy metals (HMs) were determined using the modified BCR (Community Bureau of Reference) sequential extraction procedure, before and after EDTA extraction. The results indicated that EDTA was an effective extractant because of its strong chelating ability for various HMs. The proportions of Pb, Zn, Cu and Cd in the four fractions varied largely after EDTA extraction. The extraction efficiency of EDTA of the acid-extractable fraction (AEX) was significant in shallow soil column, while in deeper soil column, decrease of the extraction efficiency of reduced (RED), oxidizable (OX) and residual fractions (RES) was obtained, which was mainly due to the decrease of EDTA concentration. [Copyright &y& Elsevier]

Abstract: Different edible tissues of citrus fruit, namely juice sacs (JS), segment membrane (SM), and segment (Seg), of four species, were examined for contents of bioactive compounds and total antioxidant capacities (TAC) by ferric reducing antioxidant power (FRAP) assay. Two flavanones (naringin and hesperidin) were identified by HPLC; hesperidin accounted for 18.5–38.5% of the total phenolics in the species Citrus unshiu, Citrus reticulata, and Citrus sinensis, while naringin was only found in Citrus changshanensis and it accounted for 53.7% of the total phenolics in SM of this species. In SM of all selected species, the contents of phenolic compounds and TAC were significantly higher than those in JS and Seg. Highest total phenolics, total flavonoids, naringin, and TAC were found in SM of C. changshanensis, while the highest carotenoid content was found in JS of C. reticulata. The contribution of vitamin C to TAC ranged from 26.9% to 45.9% in JS and Seg of all selected species. In SM, however, a high contribution from hesperidin was observed in C. unshiu (54.0%), C. sinensis (46.7%) and C. reticulata (30.0%). The results indicated that SM of citrus fruit were high in contents of bioactive compounds and TAC; it is thus recommended to consume citrus fruit with all edible tissues rather than juice or JS alone. [Copyright &y& Elsevier]

Abstract: Chilling injury occurs in loquat (Eriobotrya japonica Lindl. cv. Luoyangqing) fruit when they are stored at temperatures lower than 5°C. In attempts to reduce this chilling injury, the effect of low temperature conditioning (LTC) was examined. Loquat fruit were conditioned at 5°C for 6 days before 0°C storage for up to 54 days. Control fruit stored at 0°C exhibited severe symptoms of lignification and tissue browning, and a decrease in percentage juice. LTC treatment significantly reduced these chilling injury symptoms, and doubled storage life. In terms of acceptability (tissue browning, internal browning (IB) index <0.4; fruit decay, <10%; flesh firmness, <6.0N; percentage juice, >60%), fruit could only be stored for 40 days at 0°C with a 3 days shelf life at 20°C, while LTC fruit could be stored for 60 days at 0°C with a similar shelf life. Similarly, LTC fruit could be stored for 40 days with a 5 days shelf life at 20°C, while fruit could be only stored for 20 days at 0°C with a 5 days shelf life. Our results confirm that LTC can effectively alleviate postharvest chilling injury of loquat fruit and may provide longer storage life with acceptable external and internal quality. [Copyright &y& Elsevier]

Abstract: The postharvest responses of Chinese bayberry (Myrica rubra Sieb. & Zucc.) at 20°C were investigated using three red cultivars, ‘Biqi’, ‘Hunanzhong’ and ‘Wuzhong’. Fruit from a single harvest for each cultivar were divided into three categories according to fruit colour, designated as ‘immature’, ‘mature’ and ‘ripe’. Respiration rate, ethylene production, total soluble solids (TSS), titratable acidity (TA), fructose, glucose, sucrose and individual organic acids contents were determined over 48h at 20°C after harvest. Immature and mature fruit of all three cultivars underwent typical climacteric respiratory and ethylene behaviour, while ripe fruit did not exhibit any climacteric rise. TSS, TA, sugar and organic acid contents of all three cultivars substantially declined over the 48h; changes in the ratios of TSS/TA and SS/organic acids indicated that acid content decreased more rapidly than sugar content. Citric, malic, oxalic and tartaric acids were the principle organic acids detected, and sugars were mainly sucrose, glucose and fructose. ‘Biqi’ and ‘Hunanzhong’ cultivars had very similar levels of sugars and acids, whereas the ‘Wuzhong’ cultivar had lower levels of both components. Postharvest life could be extended for up to 7 days by storage at 0°C, but with only a short subsequent shelf life because of rot development. Chinese bayberry fruit should be classified as a climacteric fruit, and our results show the importance of fruit maturity in terms of postharvest response, and similar patterns of response among the three cultivars. [Copyright &y& Elsevier]