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Nierji Reservoir is the largest and most important water conservancy project in the Nenjiang River Basin. A thorough understanding of variations in streamflow and the driving factors of the Nierji Reservoir Basin (NERB) is crucial, but there are still gaps. In this paper, the annual streamflow data of Nierji Reservoir from 1898 to 2013 were applied to detect changing trends and abrupt changes using the Mann–Kendall method. Additionally, a Back Propagation–Artificial Neural Network (BP-ANN) model was developed to explore the relationships between the streamflow and its influencing factors and further quantify the relative contribution of each factor to the streamflow change. The results revealed that the annual streamflow of NERB significantly increased from 1898 to 2013 but declined during 1988–2013. Human activities were found to be the primary driver of streamflow decrease during 1988–2013 (nearly 75% of the total change). GDP had the largest influence, contributing 32% to the overall variation. Forest area, precipitation, and cultivated area had contributions of 25%, 23%, and 18%, respectively. Temperature had the least impact, with a relative contribution of 2%. This study provides valuable insights into water resources management in the Nenjiang River Basin, benefiting both agriculture and ecology. HIGHLIGHTS Inter- and intra-annual variability of streamflow in the NERB was analyzed.; The BP-ANN model can properly simulate the relationship between streamflow and its influencing factors.; Annual streamflow showed different trends in different periods.; Much of the streamflow decrease during 1988–2013 was attributed to human activities.; It provides valuable information for water resources management in the lower Nenjiang River Basin.;

Abstract Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis. This susceptibility is mediated by activation of the MEK/ERK/SRF pathway. SRF is a crucial transcription factor that increases AGPS transcription by binding to the AGPS promoter region. Moreover, the results demonstrated that CagA-positive cells are more sensitive to apatinib than are CagA-negative cells, suggesting that detecting the H. pylori CagA status may aid patient stratification for treatment with apatinib.

Rotary drilling has been recognized for its excellent drilling performance in laser drilling. However, there are few studies on the optical path trajectory equations guiding the implementation of laser rotary drilling, which has limited the development of rotary drilling. Here, the paper deduces the optical path trajectory equations by combining spatial vectors based on the three optical wedges laser drilling platform. Then, the influence of the parameters in the equation on the microhole and drilling path is discussed by using the control variable method. The results show that the three optical wedges systems can have a good drilling ability by using the parameters obtained from the optical path trajectory equations.

Objectives: Previous studies suggested protective associations of vegetables and fruits (VF) intake with cognitive function, but evidence on specific types of VF was insufficient. Methods: The current study included 4066 participants from 1997 to 2006 in the China Health and Nutrition Survey (CHNS) and 6170 participants from 2013 to 2020 in the Health and Retirement Study (HRS). Dietary intake (using 3-day 24-h dietary recalls in CHNS and food frequency questionnaire in HRS) and cognitive function (using the Telephone Interview for Cognitive Status-Modified, TICS-m) were measured. Linear mixed-effects models were used to estimate the beta coefficients (β) and the 95% confidence intervals (CI) to evaluate the association of VF with cognitive function (z-score) and its decline. Results: Highest intake of total VF was associated with better cognitive function and slower cognitive decline. Differences in cognitive function z-score between the highest and lowest tertiles of VF consumption were 0.039 (95% CI: 0.002, 0.076) for CHNS and 0.063 (95% CI: 0.026, 0.100) for HRS. The corresponding differences in annual cognitive decline were 0.011 (95% CI: 0.002, 0.021) and 0.012 (95% CI: 0.003, 0.020) units respectively. Vegetables and fruits showed independent associations with cognitive function and its decline. In specific VF subgroups, when comparing the highest to the lowest tertile intake, cruciferous vegetables (β = 0.058, 95% CI: 0.017, 0.100 in CHNS and β = 0.067, 95% CI: 0.032, 0.101 in HRS) and green leafy vegetables (β = 0.036, 95% CI: −0.001, 0.073 in CHNS and β = 0.082, 95% CI: 0.046, 0.117 in HRS) was associated with better cognitive function in both cohorts. Similarly, higher intake of dark-colored vegetables (β = 0.019, 95% CI: 0.008, 0.030 for red/yellow vegetables in CHNS and β = 0.004, 95% CI: 0.001, 0.007 for green leafy vegetables in HRS) were associated with slower cognitive decline in subsequent years. Moreover, rigorous sensitivity analyses confirmed the stability of the results. Conclusions: Our findings support the potential beneficial roles of VF, especially cruciferous vegetables, green leafy vegetables, and red/yellow vegetables, in maintaining cognitive function and slowing cognitive decline in middle-aged and older adults.

Different from the true oyster (family Ostreidae), the molecular diversity of the gryphaeid oyster (family Gryphaeidae) has never been sufficiently investigated. In the present study, the complete mitochondrial (mt) genome of Hyotissa sinensis was sequenced and compared with those of other ostreoids. The total length of H. sinensis mtDNA is 30,385 bp, encoding 12 protein-coding-genes (PCGs), 26 transfer RNA (tRNA) genes and two ribosomal RNA (rRNA) genes. The nucleotide composition and codon usage preference of H. sinensis mtDNA is similar to that of H. hyotis within the same genus. On the other hand, the presence of three trnM and three trnL genes of H. sinensis was not detected neither in H. hyotis nor other ostroid species. Another unique character of H. sinensis mtDNA is that both rrnS and rrnL have a nearly identical duplication. The PCG order of H. sinensis is identical to H. hyotis and the two congener species also share an identical block of 12 tRNA genes. The tRNA rearrangements mostly happen in the region from Cox1 to Nad3, the same area where the duplicated genes are located. The rearrangements within Gryphaeidae could be explained by a "repeat-random loss model". Phylogenetic analyses revealed Gryphaeidae formed by H. sinensis + H. hyotis as sister to Ostreidae, whereas the phylogenetic relationship within the latter group remains unresolved. The present study indicated the mitogenomic diversity within Gryphaeidae and could also provide important data for future better understanding the gene order rearrangements within superfamily Ostreoidea.

Abstract Background Previous studies have revealed that sodium-restricted diet intervention significantly decreased apnea frequency among patients with sleep apnea. However, the longitudinal association between the habit of adding salt to foods and sleep apnea in general populations is uncertain. Methods The UK Biobank cohort study includes more than 500,000 participants aged 40 to 69 across the United Kingdom from 2006 to 2010. The frequency of adding salt to foods was collected through a touch screen questionnaire. Incident sleep apnea was ascertained by hospital inpatient records, death registries, primary care, and self-reported diagnosis. The association between the habit of adding salt to foods and incident sleep apnea was estimated using Cox proportional hazard regression models. Results Among the 488,196 participants (mean age 56.5 years; 55.0% female) in this study. During a median follow-up of 12.3 years, 6394 sleep apnea events occurred. Compared to participants who never/rarely added salt to foods, those who sometimes, usually, and always added salt to foods had an 11% (hazard ratio [HR] 1.11, 95% confidence interval [CI]: 1.04 to 1.17), 15% (HR 1.15, 95% CI: 1.07 to 1.24), and 24% (HR 1.24, 95% CI: 1.12 to 1.37) higher risk for incident sleep apnea, respectively. Conclusions In this large prospective study, the habit of adding salt to foods was associated with a higher risk of incident sleep apnea. The findings support the benefits of a salt reduction program in preventing sleep apnea.

Abstract Background Adding salt at the table is a prevalent eating habit, but its long-term relationship with cardiovascular disease (CVD) and all-cause mortality remains unclear. We evaluated the associations of adding salt at the table with the risk of incident CVD and all-cause mortality. Methods Among 413,109 middle- and old-aged adults without cancer or CVD, all participants reported the frequency of adding salt at the table at baseline. The associations between adding salt at the table and incident CVD (the composite endpoint of coronary heart disease, stroke, heart failure, and CVD deaths) and all-cause mortality were investigated using Cox proportional hazards models. Results Of the study population, the mean age was 55.8 years and 45.5% were men; 44.4% reported adding salt at the table; 4.8% reported always adding salt at the table. During a median follow-up of 12 years, there were 37,091 incident CVD cases and 21,293 all-cause deaths. After adjustment for demographic, lifestyle, and cardiometabolic risk factors, the multivariable-adjusted hazard ratios (HRs) for participants who always added salt at the table versus never/rarely added salt at the table were 1.21 (95% confidence interval [CI]: 1.16-1.26) for CVD, 1.19 (95%CI: 1.05–1.35) for CVD mortality, and 1.22 (95%CI: 1.16–1.29) for all-cause mortality, respectively. Conclusions In this prospective cohort study, a higher frequency of adding salt at the table was associated with a greater risk of incident CVD and mortality. Our findings support the benefits of restricting the habit of adding salt at the table in promoting cardiovascular health.

Abstract Anti‐angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is a major cause for the failure of anti‐angiogenic therapy, but the underlying mechanism remains unclear. Here, it is revealed that N4‐acetylcytidine (ac4C), a newly identified mRNA modification, enhances hypoxia tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription is regulated by HIF‐1α, a key transcription factor of the cellular response to hypoxia. Further, acRIP‐sequencing, Ribosome profiling sequencing, RNA‐sequencing, and functional studies confirm that NAT10 in turn activates the HIF‐1 pathway and subsequent glucose metabolism reprogramming by mediating SEPT9 mRNA ac4C modification. The formation of the NAT10/SEPT9/HIF‐1α positive feedback loop leads to excessive activation of the HIF‐1 pathway and induces glycolysis addiction. Combined anti‐angiogenesis and ac4C inhibition attenuate hypoxia tolerance and inhibit tumor progression in vivo. This study highlights the critical roles of ac4C in the regulation of glycolysis addiction and proposes a promising strategy to overcome resistance to anti‐angiogenic therapy by combining apatinib with ac4C inhibition.

Abstract Background Although the anti-programmed death-1 (PD-1) inhibitor plus chemotherapy combination has been approved as the standard first-line treatment for advanced gastric cancer, a proportion of patients do not significantly benefit from this therapy. Who would respond poorly to this treatment and the underlying mechanisms of treatment failure are far from clear. Methods We retrospectively analyzed the associations between the peripheral basophils at baseline and clinical outcomes in 63 advanced gastric cancer patients treated with anti-PD-1 plus chemotherapy and 54 patients treated with chemotherapy alone. Immunohistochemistry and immunofluorescence staining in gastric cancer samples were utilized to investigate the basophil-related immunophenotype. Results The optimal cutoff of basophil count to distinguish responders to anti-PD-1 plus chemotherapy from non-responders was 20.0/μL. Compared with the low basophil group (≤ 20.0/μL, n = 40), the high basophil group (> 20.0/μL, n = 23) had a significantly lower objective response rate (ORR 17.4% vs. 67.5%, p = 0.0001), worse progression-free survival (median PFS 4.0 vs. 15.0 months, p = 0.0003), and worse overall survival (median OS not reached, p = 0.027). Multivariate analyses identified a basophil count of > 20.0/μL as an independent risk factor for a worse ORR (OR 0.040, 95% CI 0.007–0.241, p = 0.0004), worse PFS (HR 3.720, 95% CI 1.823–7.594, p = 0.0003) and worse OS (HR 3.427, 95% CI 1.698–6.917, p = 0.001). In contrast, there was no significant association between peripheral basophil counts and tumor response or survival in the chemotherapy-alone group (p > 0.05). In primary gastric cancer samples, we observed a correlation between higher peripheral basophil counts and the accumulation of tumor-infiltrating basophils (r = 0.6833, p = 0.005). Tumor-infiltrating basophils were found to be spatially proximate to M2 macrophages within TME and positively correlated with tumor M2 macrophage infiltration (r = 0.7234, p = 0.0023). The peripheral basophil counts also had a significant positive correlation with tumor-infiltrating M2 macrophage counts (r = 0.6584, p = 0.003). Further validation in tumor samples treated with the neoadjuvant anti-PD-1 inhibitor plus chemotherapy combination suggests that the peripheral basophils, tumor infiltration of basophils, and M2 macrophages were significantly more abundant in non-responders than in responders (p = 0.0333, p = 0.0007, and p = 0.0066, respectively). Conclusions The peripheral basophil count was observed to be a potential biomarker of anti-PD-1 efficacy for advanced gastric cancer. Moreover, basophils may induce an immune-evasive tumor microenvironment by increasing M2 macrophage infiltration, which could be a potential immunotherapeutic target for advanced gastric cancer.

The Tonnoidea Suter, 1913 (1825) is a moderately diverse group of large predatory gastropods, the systematics of which remain unclear. In the present study, the complete mitochondrial genomes of nine Tonnoidean species were sequenced. All newly sequenced mitogenomes contain 13 protein-coding genes (PCGs), 22 transfer RNA genes and two ribosomal RNA genes, showing similar patterns in genome size, gene order and nucleotide composition. The ratio of nonsynonymous to synonymous of PCGs indicated that NADH complex genes of Tonnoideans were experiencing a more relaxed purifying selection compared with the COX genes. The reconstructed phylogeny based on the combined amino acid sequences of 13 protein-coding genes and the nucleotide sequences of two rRNA genes supported that Ficidae Meek, 1864 (1840) is a sister to Tonnoidea. The monophylies of all Tonnoidean families were recovered and the internal phylogenetic relationships were consistent with the current classification. The phylogeny also revealed that Tutufa rebuta (Linnaeus, 1758) is composed of at least two different species, indicating that the species diversity within Bursidae Thiele, 1925 might be underestimated. The present study contributes to the understanding of the Tonnoidean systematics, and it could provide important information for the revision of Tonnoidean systematics in the future.

The complete mitogenomes of Pinctada albina and Pinctada margaritifera were sequenced in this study, with sizes of 23,841 bp and 15,556 bp, respectively. The mitochondrial genome analysis of eight Pterioidea species indicated the existence of gene rearrangements within the superfamily. The ATP8 gene was not detected in the two new mitogenomes, and rrnS was found to be duplicated in P. albina’s mitogenome. The reconstructed phylogeny based on mitogenomes strongly supported the monophyly of Pterioidea and provided robust statistical evidence of the phylogenetic relationships within Pteriomorphia. The analysis of the mitochondrial gene order revealed that of P. margaritifera to be the same as the ancestral order of Pterioidea. The gene orders of the Pterioidea species were mapped to the phylogenetic tree, and the gene rearrangement events were inferred. These results provide important insights that will support future research, such as studies extending the evolutionary patterns of the gene order from P. margaritifera to other species and determining the evolutionary status of Pterioidea within the infraclass Pteriomorphia.

Association of tumor microenvironment and immune checkpoint (e.g., PD-L1) is important for immune escape, impacting chemotherapy and immunotherapy efficacy. We aimed to investigate biomarkers and therapeutic targets against treatment resistance in gastric cancer. Abundances of tumor-infiltrating immune cells were estimated in multiple datasets. Three patient subgroups (A, B, and C) were identified based on seven types of PD-L1- and IFN-γ-associated immune cells. Patients yielded increased prognosis from subgroup A to C (p = 0.027). Subgroup A was characterized by high activated CD4+ memory T cell infiltration, while more resting CD4+ memory T cells were in subgroup C. Further, a risk score was developed for prognostication. Lipoma preferred partner (LPP), as the hub gene in subgroup-related regulatory network, was upregulated (p < 0.01) and was associated with high risk score (p < 0.001) and poor survival (p < 0.05). Bioinformatics analyses and experiments found that LPP expressed restrictively in fibroblasts and associated with activated CD4+ memory T cell infiltration and tumor growth. High-LPP patients yielded fewer benefits from chemotherapy or immunotherapy, compared with the low-LPP group. We finally identified 28 compounds as sensitive drugs for high-LPP patients. Our findings suggested LPP might be a biomarker for treatment response and therapeutic target in gastric cancer.

Cowries (Family Cypraeidae) are widely distributed in tropical and subtropical seas, with the highest diversity of cowries in the Indo-Pacific region. However, the classification of Cypraeidae, especially at the lower taxonomic levels, is still controversial. In the present study, we determined the complete mitochondrial genomes of 10 cowries. All the newly sequenced mtDNA encode 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and several non-coding regions. The reconstructed mitogenomic phylogeny of Cypraeidae recognized two monophyletic clades, with the first clade comprised of Erroneinae, Cypraeinae and Luriinae and the second clade formed by the single subfamily Erosarinae. The congeneric genetic distance values fall within 0.118–0.144, lower than those above genus level ranging from 0.163 to 0.271, consistent with the current division of genera within Cypraeidae. The divergence time estimated here indicated that the ancestor of Indo-Pacific cowries diversified during the Paleocene, and the closure of the Tethys Seaway might lead to the speciation events of several Indo-Pacific species. This study suggests that the complete mtDNA is a promising tool to improve the phylogenetic resolution of Cypraeidae, and mtDNA could also provide important information for future species delimitation especially within the cowries that possess different morphological phenotypes.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.MethodsWe retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.ResultsOverall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].ConclusionsLaparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.

BackgroundThe specific efficacy of immunotherapy for patients with liver metastases of gastric cancer is unclear. This study set out to explore the treatment response and related prognostic factors for patients with liver metastases of gastric cancer treated with immunotherapy.Patients and methodsThis retrospective cohort study included 135 patients with unresectable advanced gastric cancer. According to the presence of liver metastases and/or first-line treatment with immunotherapy, patients were divided into the following three groups: I-LM(-) group(patients without liver metastases treated with immunotherapy, n=66), I-LM(+) group(patients with liver metastases treated with immunotherapy, n=36), C-LM(+) group(patients with liver metastases treated with chemotherapy and/or target therapy, n=33). Cox regression analyses were used to identify factors associated with survival in all patients and the three groups, respectively.ResultsFor the patients with liver metastases treated with immunotherapy, multivariate analysis showed that only the presence of peritoneal metastases was significantly associated with shorter PFS [hazard ratios (HR), 3.23; 95% CI, 1.12-9.32; P=0.030] and the patients with peritoneal metastases had shorter median PFS than patients without peritoneal metastases(3.1 vs 18.4 months; P=0.004), while the objective response rate was 100% in patients with HER2-positive (2 complete radiographic responses and 2 partial responses; 3 of 4 patients were still ongoing benefits [median follow-up time, 15.3 months ; interquartile range(IQR), 6.3-17.9 months]).ConclusionsThe findings suggest that patients with various types of gastric cancer liver metastases respond differently to immune checkpoint inhibitors, HER2-positive patients may derive clinical benefits from immune checkpoint inhibitors, while the presence of peritoneal metastases is associated with resistance.

The marine gastropod Strombidae is widely distributed in tropical and subtropical regions all over the world and possesses high morphological diversity. In order to better understand how morphological characteristics evolved within Strombidae, a robust phylogenetic framework is needed. In the present study, the complete mitochondrial genomes of Lentigo lentiginosus, Euprotomus aratrum, and Canarium labiatum were sequenced. The three newly sequenced mt genomes contained 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and several non-coding regions, indicating a similar pattern with respect to genome size, gene order, and nucleotide composition compared with those of other strombids reported before. Two different datasets derived from mitochondrial genes were constructed to resolve the internal phylogenetic relationships of Stromboidea and Strombidae. Within Stromboidea, the sister group formed by Clade I [Rostellariidae + (Seraphsidae + Strombidae)] and Clade II [Xenophoridae + (Struthiolariidae + Aporrhaidae)] were fully recovered and supported by morphological synapomorphies as previously suggested. The phylogenetic positions of L. lentiginosus, E. aratrum, and C. labiatum were confirmed within Strombidae, and several morphological similarities were observed corresponding to the present phylogeny. A correlation between strombids speciation events and paleoclimate change was presumed. Our results indicate that complete mt genomes would be a promising tool to reconstruct a robust phylogeny of Strombidae with an increased taxon sampling in the future.

The recent applications of Unmanned Aerial Vehicles (UAVs) and Remotely Piloted Air Systems (RPAS) often require reliable and fast two-way communications between UAVs, base stations and consumers using terrestrial cellular networks. Two crucial questions are whether existing ground networks can effectively interact with UAVs in three-dimensional space during intensive traffic and under what data transmission modes it is possible to provide the necessary Quality of Service (QoS). To answer this question, the UAV/RPAS communication channel model “BS-ATM-HUB-RPAS” with a ground network was designed and investigated. The dependencies of dropped packets, message Travel Time (TT) and HUB Average Utilization on the Transaction Size (TS), the link bandwidth, the Bit Error Rate (BER) and the Packet Fail Chance for different distribution laws of Time Between Transactions (TBT) were analyzed. A significant benefit has been observed in using the LogNormal TBT distribution law rather than the Const and Exponential TBT distributions for the dependencies of dropped packets versus TS, HUB Average Utilization versus TS, and HUB Average Utilization versus link bandwidth. However, for the dependency of message Travel Time on the Transaction Size, the type of TBT distribution did not play a significant role; for all distributions, with increasing transaction size, the time of their transmission via the channel was increased. The importance and usefulness of such a numerical analysis lies in the ability to set traffic parameters and observe the resulting throughput, packet loss, and number of bit errors and QoS in a channel under certain transmission modes.

As theories evolve, the mechanism of glioma origination remains poorly understood. Understanding this mechanism promotes the clinical research on glioma therapeutic strategy and then improves the prognosis of patients with glioma. However, the overall survival of these patients is unsatisfactory. In the recent decade, a few novel therapies, such as tumor-treating fields and immunotherapy, have been introduced in clinic. Before they can be widely used, many key factors, including efficacy, safety, and benefit ratio, should be fully evaluated. Therefore, more clinical trials are required to corroborate the results and conclusions of basic research and improve the current treatment strategies. In this article, we searched relevant literature published in the past 5 years in PubMed and China National Knowledge Infrastructure and reviewed the advancements of clinical therapeutic research on glioma.

The mitochondrial (mt) genome is an important tool when studying the evolution of metazoan animals. The oyster family Gryphaeidae, together with Ostreidae, is one of the two extant taxa of superfamily Ostreoidea. Up until now, the available mitochondrial genomes of oysters were all limited to family Ostreidae. In the present study, the first complete mtDNA of family Gryphaeidae represented by Hyotissa hyotis was sequenced and compared with other available ostreoid mtDNA. The mtDNA of H. hyotis is 22,185 bp in length, encoding 13 protein-coding-genes (PCGs), two ribosomal RNA (rRNA) and 23 transfer RNA (tRNA) genes. Within all the intergenic regions that range from 2 to 1528 bp, two large non-coding regions were identified. The first large non-coding region, located between Cox1 and trnA, contains 1528 nucleotides, while the second one is 1191 bp in length and positioned between Cytb and Nad2. The nucleotide composition of the whole mtDNA is A + T biased, accounting for 59.2%, with a negative AT skew value of −0.20 and a positive GC skew value of 0.33. In contrast to the mtDNA of Ostreidae, neither the split of rrnL nor rrnS was detected in that of H. hyotis. The duplication of trnW of H. hyotis was also discovered for the first time within Ostreoidea. The gene order of H. hyotis is quite different from those of ostreids, indicating extensive rearrangements within superfamily Ostreoidea. The reconstructed phylogeny supported H. hyotis as sister to Ostreidae, with the latter clade formed by Ostrea + (Saccostrea + Crassostrea). This study could provide important information for further understanding the mitochondrial evolution of oysters.

In this paper, transient electromagnetic response excited by ramp-shaped current using a conical source is studied for the sensing of underground environments. The transient time responses from the conical source with either multi-turn coils or a single loop coil are investigated and compared. Although with the same magnetic moment, the turn-off time for conical source is longer than that of the single loop-this is due to the fact that the time of entering different testing stages using a multi-turn coil system is often earlier than that for a single loop system. To correct turn-off error, the conical source type transmitter is used and the one-dimensional modeling of a layered media, in which the calculation of the turn-off response is carried over the entire time range by solving directly an upper limit-variable integral. The turn-off correction method matched the resistivity and the layer thickness, which is critical for the detection of shallow depth problems. Finally, a field example is presented to illustrate the effect of turn-off time on the interpretation of transient sounding data for a conical source system.

In the field of human health monitoring, intelligent diagnostic methods have drawn much attention recently to tackle the health problems and challenges faced by patients. In this paper, an efficient and flexible diagnostic method is proposed, which enables the simultaneous use of a machine learning method and sparsity-based representation technique. Specifically, the proposed method is based on a convolutional neural network (CNN) and generalized minimax-concave (GMC) method. First, measured potential signals, for instance, electroencephalogram (EEG) and electrocardiogram (ECG) signals are directly inputted into the designed network based on CNN for health conditions classification. The designed network adopts small convolution kernels to enhance the performance of feature extraction. In the training process, small batch samples are applied to improve the generalization of the model. Meanwhile, the “Dropout” strategy is applied to overcome the overfitting problem in fully connected layers. Then, for a record of the interested EEG or ECG signal, the sparse representation of useful time-frequency features can be estimated via the GMC method. Case studies of seizure detection and arrhythmia signal analysis are adopted to verify the performance of the proposed method. The experimental results demonstrate that the proposed method can effectively identify different health conditions and maximally enhance the sparsity of time-frequency features.

Titanium alloy is a type of high-strength material that is difficult to process. In particular, in the aerospace field, the processing accuracy of titanium alloy is high. Recently, laser processing has emerged as a new technology with high processing precision. However, the laser processing methods have obvious differences in processing accuracy and effect. Among them, the laser spiral scanning method plays an important role in welding and drilling, but owing to the complexity of the laser molten pool behavior, there have been limited studies on the material removal mechanism based on laser spiral scanning. To understand the variable process of titanium alloy melt pool in laser spiral scanning processing, a light heat conduction model with mass transfer source term was simulated. The effects of laser power, scanning speed, and scanning path on the morphology were studied. The simulation results show that the unit energy density was the main factor for material removal, and the distribution of the material temperature affected the size of the recast layer. The experimental and simulation results were compared, and good agreement between them was observed. This study can provide a research foundation for the further application of laser spiral scanning technology.

IL13Rα2 is a cell surface tumor antigen that is overexpressed in multiple tumor types. Here, we studied biodistribution and targeting potential of an anti-IL13Rα2 antibody (Ab) and anti-tumor activity of anti-IL13Rα2-antibody-drug conjugate (ADC). The anti-IL13Rα2 Ab was labeled with fluorophore AF680 or radioisotope 89Zr for in vivo tracking using fluorescence molecular tomography (FMT) or positron emission tomography (PET) imaging, respectively. Both imaging modalities showed that the tumor was the major uptake site for anti-IL13Rα2-Ab, with peak uptake of 5–8% ID and 10% ID/g as quantified from FMT and PET, respectively. Pharmacological in vivo competition with excess of unlabeled anti-IL13Rα2-Ab significantly reduced the tumor uptake, indicative of antigen-specific tumor accumulation. Further, FMT imaging demonstrated similar biodistribution and pharmacokinetic profiles of an auristatin-conjugated anti-IL13Rα2-ADC as compared to the parental Ab. Finally, the anti-IL13Rα2-ADC exhibited a dose-dependent anti-tumor effect on A375 xenografts, with 90% complete responders at a dose of 3 mg/kg. Taken together, both FMT and PET showed a favorable biodistribution profile for anti-IL13Rα2-Ab/ADC, along with antigen-specific tumor targeting and excellent therapeutic efficacy in the A375 xenograft model. This work shows the great potential of this anti-IL13Rα2-ADC as a targeted anti-cancer agent.

The spike protein (S) plays a crucial role in porcine epidemic diarrhea virus (PEDV) infection and induces neutralizing antibodies. Mutations of the S protein are supposed to provide the main antigenic shift leading to the antigenic escape of PEDVs. It is therefore a significant question how much accumulation of antigenic shift could lead to the antigenic escape of the variant PEDV. To provide an answer in the study, B cell epitopes (BCEs) on the S protein of the PEDV vaccine strain CV777 (SCV777) and variant strain SD2014 (SSD2014) were mapped using biosynthetic peptides and rabbit anti-PEDV S serum. Seventy-nine and 68 linear BCEs were identified from SCV777 and SSD2014, respectively. While 66.2% of the BCEs of SSD2014 could be recognized by anti-SCV777 serum and 67.1% of SCV777 BCEs could be recognized by anti-SSD2014 serum, more than 40% of the BCEs identified using anti-SCV777 serum on SCV777 could not be recognized by anti-SSD2014 serum and vice versa. The completely shared BCEs took low percentages of 29.4% and 25.3% for SSD2014 and SCV777, respectively. These results indicate a low conservation of antigenicity of the S protein compared to a relatively high amino acid sequence similarity of 92.2% between the two strains. The study provided a BCE shift reference of PEDV antigenic escape and surveillance control.

Flexible pressure sensors have received much attention due to their widespread potential applications in electronic skins, health monitoring, and human–machine interfaces. Graphene and its derivatives hold great promise for two-dimensional sensing materials, owing to their superior properties, such as atomically thin, transparent, and flexible structure. The high performance of most graphene-based pressure piezoresistive sensors relies excessively on the preparation of complex, post-growth transfer processes. However, the majority of dielectric substrates cannot hold in high temperatures, which can induce contamination and structural defects. Herein, a credibility strategy is reported for directly growing high-quality vertical graphene (VG) on a flexible and stretchable mica paper dielectric substrate with individual interdigital electrodes in plasma-enhanced chemical vapor deposition (PECVD), which assists in inducing electric field, resulting in a flexible, touchable pressure sensor with low power consumption and portability. Benefitting from its vertically directed graphene microstructure, the graphene-based sensor shows superior properties of high sensitivity (4.84 KPa−1) and a maximum pressure range of 120 KPa, as well as strong stability (5000 cycles), which makes it possible to detect small pulse pressure and provide options for preparation of pressure sensors in the future.

Abstract Background Patient-derived xenografts (PDX) have a biologically stable in tumor architecture, drug responsiveness, mutational status and global gene-expression patterns. Numerous PDX models have been established to date, however their thorough characterization regarding the tumor formation and rates of tumor growth in the established models remains a challenging task. Our study aimed to provide more detailed information for establishing the PDX models successfully and effectively. Methods We transplanted four different types of solid tumors from 108 Chinese patients, including 21 glioblastoma (GBM), 11 lung cancers (LC), 54 gastric cancers (GC) and 21 colorectal cancers (CRC), and took tumor tissues passaged for three successive generations. Here we report the rate of tumor formation, tumor-forming times, tumor growth curves and mortality of mice in PDX model. We also report H&E staining and immunohistochemistry for HLA-A, CD45, Ki67, GFAP, and CEA protein expression between patient cancer tissues and PDX models. Results Tumor formation rate increased significantly in subsequent tumor generations. Also, the survival rates of GC and CRC were remarkably higher than GBM and LC. As for the time required for the formation of tumors, which reflects the tumor growth rate, indicated that tumor growth rate always increased as the generation number increased. The tumor growth curves also illustrate this law. Similarly, the survival rate of PDX mice gradually improved with the increased generation number in GC and CRC. And generally, there was more proliferation (Ki67+) in the PDX models than in the patient tumors, which was in accordance with the results of tumor growth rate. The histological findings confirm similar histological architecture and degrees of differentiation between patient cancer tissues and PDX models with statistical analysis by GraphPad Prism 5.0. Conclusion We established four different types of PDX models successfully, and our results add to the current understanding of the establishment of PDX models and may contribute to the extension of application of different types of PDX models.

A quickly tunable wettability pattern plays an important role in regulating the surface behavior of liquids. Light irradiation can effectively control the pattern to achieve a specific wettability pattern on the photoresponsive material. However, metal oxide materials based on light adjustable wettability have a low regulation efficiency. In this paper, zinc (Zn) superhydrophobic surfaces can be obtained by femtosecond-laser-ablated microholes. Owing to ultraviolet (UV) irradiation increasing the surface energy of Zn and heating water temperature decreasing the surface energy of water, the wettability of Zn can be quickly tuned photothermally. Then, the Zn superhydrophobic surfaces can be restored by heating in the dark. Moreover, by tuning the pattern of UV irradiation, a specific wettability pattern can be transferred by the Zn microholes, which has a potential application value in the field of new location-controlled micro-/nanofluidic devices, such as microreactors and lab-on-chip devices.

Microholes have crucial applications in aerospace, the automotive industry, and other industries. In this study, the microhole processing technology based on the femtosecond-laser spiral trepanning method was investigated. By adjusting the spiral scanning path, laser power distribution, and defocusing amount to control laser energy distribution, an inverted cone hole, straight hole, and normal cone hole were obtained finally. The morphology and element of the microhole were investigated by scanning electron microscopy (SEM) equipped with energy-dispersive X-ray spectroscopy (EDX). The experimental results of the femtosecond-laser spiral trepanning method could achieve fewer impurities. Finally, the formation mechanisms of different microholes are explained in detail. The method is simpler and more efficient than the traditional microhole processing technology. The femtosecond-laser spiral trepanning method with controllable hole roundness, accuracy, and taper has important practical significance in microhole processing.

Surface roughness and the material removal rate (MRR) are two important indicators during the grinding process. The former determines the surface quality while the latter reflects the grinding efficiency directly. In this paper, the two indicators are taken into consideration simultaneously and differently by converting them into a comprehensive goal with using weighting objective method. A prediction model was established for each comprehensive goal with each different combination of surface roughness and MRR weighting coefficient. The optimal value of abrasive size, contact force, belt linear speed, and feed speed were obtained under different grinding situations by using a central composite design (CCD) combined with response surface analysis. The experimental results showed that the comprehensive goal can be used effectively as an indicator to control the grinding performance and improve the optimization process.

The typical rise time of PTS machine is ∼110 ns with about 10 MA peak current under short pulse mode when all 24 modules discharge simultaneously. By distributing the trigger times of 12 laser beams logically and adjusting the statues of the pulse output switches, longer rise-time pulse can be obtained on the PTS facility. Based on the required pulse shape, whole circuit simulations will be used to calculate the trigger times of each laser triggering gas switch and the status of the pulse output switches. The rise time of the current is determined by the time difference between the first and last trigged laser triggering gas switches. In order to trigger the laser triggering gas switch, sufficient laser power is needed to be sent into the gap of the gas switches. The gas pressure and voltage difference on the two electrodes of the gas switches also affect the triggering of the gas switches, and the voltage added on the gas switch is determined by its transition time. Traditionally the trigger time difference should be less than the transition time of the two neighboring modules. A new simulation model of PTS shows one can break this transition time limits. Series of current pulse shaping experiments have been investigated on the PTS (Primary Test Stand). As results, more than 5 MA peak current were successfully achieved on the load with a rise time of 600 ns. This study and experiments of the pulse shaping on PTS demonstrate the adaptable ability of the PTS for offering different waveform of mega ampere current pulse for different research purpose.

Background: The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. Methods: This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan--Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. Results: Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08-0.57; P =0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56-25.36; P= 0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. Conclusions: Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased postconversion surgery recurrence. [ABSTRACT FROM AUTHOR]

Abstract Microbes are important components of the tumor microenvironment and have a close relationship with tumors. However, there is still a lack of research on the intratumoral microbiota in bladder cancer and its impact on the tumor immune microenvironment. In this study, we used fluorescence in situ hybridization (FISH) and observed a substantial presence of microbiota in bladder cancer tissues, with greater abundance compared to that in normal bladder tissues. Based on the BIC database, we found that the microbiome of bladder cancer is highly diverse and its structure is significantly different from that of other tumors. To investigate the relationships among the intratumoral microbiota, tumor immunity, and prognosis in bladder cancer patients, we analyzed bladder cancer-specific differentially expressed immune- and antimicrobial-related genes from the ImmPort, TISIDB, and TCGA databases. We identified 11 hub genes and constructed a prognostic risk model. Further analysis revealed differences at the family and genus levels between distinct groups. Using LEfSe analysis, we identified six hub biomarkers and developed a novel microbial-based scoring system. The scoring system allows subgrouping of bladder cancer patients, with significant differences in prognosis, immune cell infiltration, tumor mutation burden, and immune checkpoints among different groups. Further FISH and immunofluorescence co-staining experiments initially verified that the specific distribution of microorganisms and M2 macrophages in bladder cancer may be closely related to the poor prognosis of patients. In conclusion, this study revealed the characteristics of the intratumoral microbiota in bladder cancer and identified potential prognostic targets for clinical application.