bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation characteristics of stress distribution in the subchondral bone of the knee joint of judo athletes with long-term stress changes
Authors: Li Zhiqiang , Xu Guanghua , Wang Chengjun , Wang Qiuyuan , Liu Caiping , Guo Tingting , Wu Lijun , Cao Diankang
Published: January 2023

Objective

To investigate the distribution of bone density in the subchondral bone tissue of the knee joint due to the mechanical stress load generated by judo, the bone tissue volume of different densities and the bone remodeling characteristics of the subchondral bone of the knee joint.

Methods

CT imaging data of the knee joint were collected from 15 healthy individuals as controls and 15 elite judo athletes. Firstly, they were processed by the CTOAM technique, and secondly, the distribution pattern of high-density areas of the knee joint was localized using nine anatomical regions. In addition, three tomographic images were selected in the sagittal, coronal, and axial 2D image windows to observe the distribution of different densities of bone tissue. Finally, the percentage of bone tissue volume (%BTV) and bone remodeling trend of bone tissues with different densities were determined.

Results

In this study, high-density areas were found in the 4th, 5th, and 6th regions of the articular surface of the distal femur and the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th and 8th regions of the tibial plateau in judo athletes; the distribution of high-density areas on the articular surface of the distal femur in control subjects was similar with judo athletes, and high-density areas were mainly found in the 4th and 5th regions of the tibial plateau. The %BTV of low (401-500HU in the distal femur; 301-400 HU and 401-500HU in the tibial plateau), moderate, and high bone density was higher in judo athletes than in controls in the subchondral bone of the distal femur and tibial plateau (P< 0.05).

Conclusion

The history of compressive stresses, struck stresses, soft tissue tension and pull, self-gravity and intra-articular stress loading generated by the lower limb exercise technique of judo leads to specific forms of stress distribution and bone tissue remodeling in the subchondral bone tissue within the distal femur and tibia plateau.
LncRNA MALAT1 mediates osteogenic differentiation in osteoporosis by regulating the miR-485-5p/WNT7B axis
Authors: Zhou Yuan , Xu Zhuo , Wang Yuanyi , Song Qiang , Yin Ruofeng
Published: January 2023

Introduction

Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis.

Methods

This study aimed to investigate the effects of MALAT1 on osteogenic differentiation and cell apoptosis in osteoporosis. MALAT1 level, detected by RT-qPCR, was downregulated in hindlimb unloading (HU) mice and simulated microgravity (MG)-treated MC3T3-E1 cells. Moreover, osteogenic differentiation-related factor (Bmp4, Col1a1, and Spp1) levels were measured by RT-qPCR and Western blot. ALP activity was detected, and ALP staining was performed. Cell apoptosis was assessed by flow cytometry.

Results

The results revealed that MALAT1 upregulated the expression of Bmp4, Col1a1, and Spp1, and enhanced ALP activity. Knockdown of MALAT1 suppressed their expression and ALP activity, suggesting that MALAT1 promoted osteogenic differentiation. Additionally, MALAT1 inhibited apoptosis, increased Bax and caspase-3 levels, and decreased Bcl-2 level. However, knockdown of MALAT1 had opposite results. In MG cells, MALAT1 facilitated osteogenic differentiation and suppressed apoptosis. Furthermore, miR-485-5p was identified as a target of MALAT1, and WNT7B was verified as a target of miR-485-5p. Overexpression of miR-485-5p rescued the promotion of osteogenic differentiation and the inhibition of apoptosis induced by MALAT1. Knockdown of WNT7B abolished the facilitation of osteogenic differentiation and the suppression of apoptosis induced by downregulation of miR-485-5p.

Discussion

In conclusion, MALAT1 promoted osteogenic differentiation and inhibited cell apoptosis through the miR-485-5p/WNT7B axis, which suggested that MALAT1 is a potential target to alleviate osteoporosis.
Distribution of microbes and antimicrobial susceptibility in patients with diabetic foot infections in South China
Authors: Liu Wei , Song Liying , Sun Wei , Fang Weijin , Wang Chunjiang
Published: January 2023

Background

To investigate the distribution of microbes and drug susceptibility in patients with diabetic foot infections (DFI) and provide guidance for clinical empirical treatment and the rational selection of antibacterial drugs.

Methods

Retrospective analysis of the pathogenic bacterium distribution and antimicrobial susceptibility isolated from 581 DFI patients with different Wagner grades.

Results

The 534 positive samples included 473 cases (88.58%)) of monomicrobial infections and 61 cases (11.42%) of polymicrobial infections before antibiotic therapy. A total of 656 strains were cultivated, including 387 (58.99%) strains of gram-positive organisms (GPOs), 235 (35.82%) gram-negative bacilli (GNB), and 21 (3.20%) fungal strains. Polymicrobial infections mainly occurred in patients with Wagner grade 3-4 ulcers. GPOs were predominant in Wagner grades 1-3 (grade 1: 96.67%, grade 2: 76.52%, grade 3 62.81%), and the most common was Staphylococcus aureus (grade 1: 31.66%, grade 2: 33.04%, grade 3 35.53%). GNB were predominant in grades 4-5 (grade 4: 51.46%, grade 5:60%), and the most common GNB in Wagner grades 4-5 was Proteus (grade 4:27.88%, grade 5: 42.86%), while the most common GPO was Enterococcus (grade 4:34.48%, grade 5:25.00%). Staphylococcus (including MRSA) and Enterococcus were still highly sensitive to vancomycin, linezolid, and tigecycline. Most GNB were still highly sensitive to meropenem, tigecycline, ertapenem, and amikacin. Proteus was most sensitive to amikacin (97.14%), followed by meropenem (92%) and ertapenem (80%).

Conclusion

The distribution of microbes and antimicrobial susceptibility in DFI patients varied with different Wagner grades. The most appropriate antimicrobial therapy should be selected based on the pathogen culture and antimicrobial susceptibility.
Identifying the critical factors of transmission efficiency loss in China’s natural gas network
Authors: Wang Xiaolin , Lu Xiangyi , Zhang Xianfeng , Zeng Weijing , Liu Zhankun , Hu Xiangping
Published: January 2023

China’s market-oriented reform supports the sustainable development of energy mix and the low-carbon target, and natural gas has bridged the transition from traditional fossil energy to clean and renewable energies. The third-party access policy, launched recently by China’s natural gas market, drives the decouple between gas trade and transport. The decouple might lead to the transmission resources of physical network not optimally used, which is caused by the contractual arrangement between entry and exit capacities in commercial network. Aiming at this issue, we established a mathematical programming with equilibrium constraints (MPEC) to integrate the allocations of commercial capacity and physical flows, based on a minimum cost maximum flow problem (MCMF) abstracted from China’s existing gas network. The MPEC model was then used to strategically evaluate the transmission efficiency, and identify the critical factors of its loss. Our results show that there is transmission efficiency loss of China’s gas network from the shortage of geospatial gas supply and the invisible segmentation of gas network due to interdicted cost of pipeline, bottleneck of pipeline capacity and economic radius of gas supply chains to transport gas. Therefore, the critical factor of the loss to be identified will be helpful for strategically reducing the cost of decoupling gas trade and transport.
False data injection attack in smart grid: Attack model and reinforcement learning-based detection method
Authors: Lin Xixiang , An Dou , Cui Feifei , Zhang Feiye
Published: January 2023

The smart grid, as a cyber-physical system, is vulnerable to attacks due to the diversified and open environment. The false data injection attack (FDIA) can threaten the grid security by constructing and injecting the falsified attack vector to bypass the system detection. Due to the diversity of attacks, it is impractical to detect FDIAs by fixed methods. This paper proposed a false data injection attack model and countering detection methods based on deep reinforcement learning (DRL). First, we studied an attack model under the assumption of unlimited attack resources and information of complete topology. Different types of FDIAs are also enumerated. Then, we formulated the attack detection problem as a Markov decision process (MDP). A deep reinforcement learning-based method is proposed to detect FDIAs with a combined dynamic-static detection mechanism. To address the sparse reward problem, experiences with discrepant rewards are stored in different replay buffers to achieve efficiency. Moreover, the state space is extended by considering the most recent states to improve the perception capability. Simulations were performed on IEEE 9,14,30, and 57-bus systems, proving the validation of attack model and efficiency of detection method. Results proved efficacy of the detection method in different scenarios.
Estimation of biases and uncertainties on PWR nuclide inventories for severe accidents analyses
Authors: Ichou R. , Clavel J. B. , Bonthoux S. , Bernard F. , Taforeau J. , Malvagi F.
Published: January 2023

The work presented in this paper deals with bias and uncertainty quantification on nuclear fuel inventory in a pressurized water reactors core during normal operation. This actinides and fission products inventory is used as input data for radiological releases evaluation in case of a severe accident. The different sources of bias and uncertainty, as well as their impacts for UO2 and MOX fuel at the assembly and core levels, are discussed. Uncertainty sources include technological uncertainties (e.g. dimensions, irradiation history, temperatures), modeling assumptions, uncertainties related to the resolution methods used in the calculation tools and nuclear data uncertainties. For each source of uncertainty investigated in this paper, an evaluation of the associated biases and uncertainties on nuclide inventory is performed. It is shown that, among the sources of bias and uncertainties studied, spread due to nuclear data as well as the bias and uncertainties due to “infinite lattice approximation” are the most significant ones, for the isotopes of interest.
Modeling and analysis of factors affecting the integration of Beijing Tianjin Hebei low carbon economy based on SDM model
Authors: Zhu Lin , Wu Hua , Xu Ying
Published: January 2023

Background: Under the guidance of carbon peak and carbon neutral targets, China’s economic development is facing unprecedented challenges. It is of great strategic significance and value to study the integrated development of regional low-carbon economy. The harmonious development of Beijing-Tianjin-Hebei (Beijing-Tianjin-Hebei) has become a national strategy, and its importance is prominent.

Objective: To promote the regional economic integration of Beijing-Tianjin-Hebei is the top priority of promoting the development of Beijing-Tianjin-Hebei integration at present, and is the key to achieving the coordinated development and mutual benefit of Beijing-Tianjin-Hebei.

Methods: In this context, this paper studies the fuzzy control evaluation algorithm of regional economy based on SDM model. Realized the prediction of the expansion of the low-carbon economy in Beijing-Tianjin-Hebei, and put forward the development strategy of the economic integration of Beijing-Tianjin-Hebei. The ranking of regional competitiveness of fuzzy control evaluation method is in line with the reality of today’s economic expansion. The application of fuzzy rules improves the speed, accuracy and objectivity of evaluation.

Results: The final experiment shows that the accuracy of the algorithm is very high, reaching 95.14%. In addition, the algorithm has higher efficiency and better performance. The fuzzy control evaluation algorithm of regional economy can better predict the economic growth of Beijing, Tianjin and Hebei.

Conclusion: Propose the development strategy of Beijing-Tianjin-Hebei low-carbon economic integration to further promote the development of Beijing-Tianjin-Hebei integration and promote the adjustment and optimization of China’s economic structure.
Experimental study of rock wool on the farmland soil erosion and crop growth of winter wheat and its comprehensive evaluation
Authors: Li Wei , Liu Shanshan , Wang Yicheng , Qin Tianling , Zhang Xin , Li Chenhao , Feng Jianming
Published: January 2023

Introduction: Droughts and flooding occur frequently due to climate change and human activities, which have significantly affected the ecological environment of farmland and crop production. Rock wool (RW) has some properties like high porosity and water retention capacity, and it is widely used in green roofing and agricultural production to reduce flood and drought disaster.

Methods: We set 24 artificial rainfall experiments to analyze the impact of RW on the farmland runoff, soil water storage capacity (SWSC), nitrogen and phosphorus loss and crop growth. Finally, the Critic-Entropy comprehensive evaluation method was used to select the best solution for RW embedding.

Results: The result shows that RW could reduce the runoff by 49.6%–93.3%, and it made the SWSC increase by .2%–11% Vol in the 10–70 cm depth. During the runoff process, the concentration of nitrogen and phosphorus decreased with the increase of the RW volume, while the nitrogen and phosphorus loss reduced by 51.9%–96.6% and 72.4%–96.4% respectively when RW was buried in the farmland, so RW could effectively promote soil and water conservation. Finally, RW increased the plant biomass and yield by a maximum of 12.1% and 20.4% respectively due to the large retention of water and nutrients. Therefore, combined with the above experimental result, this study indicates that RW could obtain the best comprehensive benefit in the embedding volume of 536.73 m3/ha.

Discussion: When the volume of RW embedding was too large, RW easily caused insufficient water storage in short-duration rainfall or irrigation, which made the RW unable to release water to alleviate the soil water deficit during the critical growth period, which may result in drought events being aggravated and crop yield reduced. Overall, this study is conducive to clarifying the comprehensive application effect of RW in agricultural production, pollution control, and urban landscape, and it provides an important basis for expanding its application field and promoting the stability of farmland ecosystems.
The influence of asset specificity on farmers’ willingness to participate in fallow from the perspective of farmer differentiation
Authors: Zhang Siyang , Xie Xianxiong , Luo Yu , Liu Xiaoqi , Zhao Minjuan
Published: January 2023

Fallow is an important institutional guarantee for green agricultural development and an important measure to promote rural revitalization. Asset specificity is a crucial factor that affects farmers’ willingness to participate in fallow. In order to improve farmers’ willingness of to fallow and promote the long-term promotion of fallow system, based on the perspective of farmer differentiation, a total of 1,240 micro survey data in four cities of Gansu province was used to quantify the asset specificity by the entropy method. A multivariate ordered Logit model and a double-hurdle model were established to explore the effects of asset specificity on the willingness of farmers with different degrees of differentiation. The results show that: 1) There are differences in fallow willingness among different types of farmers. The fallow willingness of non-farmers and II part-time farmers is generally stronger than that of pure farmers and I part-time farmers. 2) Geographical location specificity has a significant negative impact on the fallow willingness of the four types of non-fallow farmers, and has significant negative impacts on the subsequent fallow willingness and fallow degree of the four types of fallow farmers. 3) Physical asset specificity has a significant negative effect on the fallow willingness of pure farmers, I part-time and II part-time farmers among non-fallow farmers, but has little effect on the subsequent fallow willingness of fallow farmers. 4) Human capital specificity has a significant negative impact on the fallow willingness of the four types of non-fallow farmers, and has a significant negative impact on the subsequent fallow willingness and fallow degree of the four types of fallow farmers.
Host vs. pathogen evolutionary arms race: Effects of exposure history on individual response to a genetically diverse pathogen
Authors: Walsh Daniel P. , Felts Brandi L. , Cassirer E. Frances , Besser Thomas E. , Jenks Jonathan A.
Published: January 2023

Introduction

Throughout their range, bighorn sheep (Ovis canadensis) populations have seen significant disease-associated declines. Unfortunately, understanding of the underlying epidemiological processes driving the disease dynamics in this species has hindered conservation efforts aimed at improving the health and long-term viability of these populations. Individual response to pathogen exposure emerges from dynamic interactions between competing evolutionary processes within the host and pathogen. The host’s adaptive immune system recognizes pathogens and mounts a defensive response. Pathogens have evolved strategies to overcome adaptive immune defenses including maintaining high genetic diversity through rapid evolution. The outcomes of this evolutionary warfare determine the success of pathogen invasion of the host and ultimately the success of conservation efforts.

Methods

During an epizootic dominated by a single strain, we explore these host-pathogen dynamics by examining the variation in effects of pathogen invasion on captive bighorn sheep with differing histories of exposure to genetically diverse strains ofMycoplasma ovipneumoniae(Movi). We monitored clinical signs of disease and sampled animals and their environment to detect spread of Movi among 37 bighorn sheep separated into nine pens based on known exposure histories.

Results

We documented Movi transmission within and across pens and we detected Movi DNA in air, water, and invertebrate samples. Higher levels of antibody to Movi prior to the epizootic were associated with a lower likelihood of presenting clinical signs of pneumonia. Nonetheless, higher antibody levels in symptomatic individuals were associated with more severe progressive disease, increased probability and speed of pneumonia-induced mortality, and reduced likelihood of returning to a healthy state. Bighorn sheep with previous exposure to a strain other than the predominant epizootic strain were more likely to recover.

Discussion

Our results indicate that Movi-strain variability was sufficient to overwhelm the adaptive host immunological defenses. This outcome indicates, in free-ranging herds, past exposure is likely insufficient to protect bighorn sheep from infection by new Movi strains, although it influences the progression of disease and recovery within the herd. Therefore, given Movi-strain variability and the lack of immunological protection from past exposure, focusing management efforts on minimizing the introduction of Movi into bighorn herds, through separation of domestic and bighorn sheep and avoidance of management activities that create commingling of bighorn sheep carrying differing Movi strains, will likely be the most effective approach for reducing the effects of disease and achieving bighorn sheep conservation goals.
Comparative genomics of Hox and ParaHox genes among major lineages of Branchiopoda with emphasis on tadpole shrimps
Authors: Nicolini Filippo , Martelossi Jacopo , Forni Giobbe , Savojardo Castrense , Mantovani Barbara , Luchetti Andrea
Published: January 2023

Hox and ParaHox genes (HPHGs) are key developmental genes that pattern regional identity along the anterior–posterior body axis of most animals. Here, we identified HPHGs in tadpole shrimps (Pancrustacea, Branchiopoda, Notostraca), an iconic example of the so-called “living fossils” and performed a comparative genomics analysis of HPHGs and the Hox cluster among major branchiopod lineages. Notostraca possess the entire Hox complement, and the Hox cluster seems to be split into two different subclusters, although we were not able to support this finding with chromosome-level assemblies. However, the genomic structure of Hox genes in Notostraca appears more derived than that of Daphnia spp., which instead retains the plesiomorphic condition of a single compact cluster. Spinicaudata and Artemia franciscana show instead a Hox cluster subdivided across two or more genomic scaffolds with some orthologs either duplicated or missing. Yet, branchiopod HPHGs are similar among the various clades in terms of both intron length and number, as well as in their pattern of molecular evolution. Sequence substitution rates are in fact generally similar for most of the branchiopod Hox genes and the few differences we found cannot be traced back to natural selection, as they are not associated with any signals of diversifying selection or substantial switches in selective modes. Altogether, these findings do not support a significant stasis in the Notostraca Hox cluster and further confirm how morphological evolution is not tightly associated with genome dynamics.
Primary sclerosing cholangitis and pancreatic cancer: A retrospective cohort study of United States veterans
Authors: Nguyen Anita , Torabi Sagvand Babak , Alizadeh Madeline , Nguyen Cydney , Scott William , von Rosenvinge Erik C.
Published: January 2023

Primary sclerosing cholangitis (PSC) is associated with hepatobiliary and colorectal cancers, but it remains uncertain if PSC increases the risk for pancreatic cancer. While some European studies have suggested an increased risk of pancreatic cancer in PSC patients, other studies have not. And these studies did not well account for presence or absence of concomitant inflammatory bowel disease (IBD). The purpose of this study is to investigate the prevalence of pancreatic cancer in United States veterans with PSC both with and without IBD.

Methods

This retrospective study used International Classification of Diseases, Tenth Revision (ICD-10) codes to identify patients with PSC, IBD, and pancreatic cancer from the Veterans Affairs (VA) Corporate Data Warehouse. The prevalence of pancreatic cancer in patients with PSC only, IBD only, PSC with IBD, and neither PSC nor IBD were compared. Logistic regression was used to control for age, gender, chronic pancreatitis, diabetes mellitus, and tobacco and alcohol use.

Results

A total of 946 patients with PSC were identified from a population of over 9 million veterans. 486 (51.4%) of these had concurrent IBD. Additionally 112,653 patients with IBD without PSC were identified. When adjusted for confounding factors, patients with PSC had a significantly higher prevalence of pancreatic cancer compared to the general population and those with IBD without PSC (2.4% vs. 0.2% and 0.5%, respectively).

Conclusions

Veterans with PSC, particularly those without concomitant IBD, have a high prevalence of pancreatic cancer compared to the general veteran population. Our findings support the need for multicenter prospective studies investigating the benefits of screening for pancreatic cancer in patients with PSC.
Potential targeted therapy based on deep insight into the relationship between the pulmonary microbiota and immune regulation in lung fibrosis
Authors: Zhang Tao , Zhang Min , Yang Liqing , Gao Lingyun , Sun Wei
Published: January 2023

Pulmonary fibrosis is an irreversible disease, and its mechanism is unclear. The lung is a vital organ connecting the respiratory tract and the outside world. The changes in lung microbiota affect the progress of lung fibrosis. The latest research showed that lung microbiota differs in healthy people, including idiopathic pulmonary fibrosis (IPF) and acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF). How to regulate the lung microbiota and whether the potential regulatory mechanism can become a necessary targeted treatment of IPF are unclear. Some studies showed that immune response and lung microbiota balance and maintain lung homeostasis. However, unbalanced lung homeostasis stimulates the immune response. The subsequent biological effects are closely related to lung fibrosis. Core fucosylation (CF), a significant protein functional modification, affects the lung microbiota. CF regulates immune protein modifications by regulating key inflammatory factors and signaling pathways generated after immune response. The treatment of immune regulation, such as antibiotic treatment, vitamin D supplementation, and exosome micro-RNAs, has achieved an initial effect in clearing the inflammatory storm induced by an immune response. Based on the above, the highlight of this review is clarifying the relationship between pulmonary microbiota and immune regulation and identifying the correlation between the two, the impact on pulmonary fibrosis, and potential therapeutic targets.
Immune cells drive new immunomodulatory therapies for myocardial infarction: From basic to clinical translation
Authors: Nian Wenjian , Huang Zijian , Fu Cong
Published: January 2023

The high incidence of heart failure secondary to myocardial infarction (MI) has been difficult to effectively address. MI causes strong aseptic inflammation, and infiltration of different immune cells and changes in the local inflammatory microenvironment play a key regulatory role in ventricular remodeling. Therefore, the possibility of improving the prognosis of MI through targeted immunity has been of interest and importance in MI. However, previously developed immune-targeted therapies have not achieved significant success in clinical trials. Here, we propose that the search for therapeutic targets from different immune cells may be more precise and lead to better clinical translation. Specifically, this review summarizes the role and potential therapeutic targets of various immune cells in ventricular remodeling after MI, especially monocytes/macrophages and neutrophils, as a way to demonstrate the importance and potential of immunomodulatory therapies for MI. In addition, we analyze the reasons for the failure of previous immunomodulatory therapies and the issues that need to be addressed, as well as the prospects and targeting strategies of using immune cells to drive novel immunomodulatory therapies, hoping to advance the development of immunomodulatory therapies by providing evidence and new ideas.
Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis
Authors: Liu Yunsong , Bao Yongxing , Yang Xu , Sun Shuang , Yuan Meng , Ma Zeliang , Zhang Wanting , Zhai Yirui , Wang Yang , Men Yu , Qin Jianjun , Xue Liyan , Wang Jun , Hui Zhouguang
Published: January 2023

Background

Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy.

Methods

A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed.

Results

A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups.

Conclusions

Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.
Impacts of river discharge, coastal geomorphology, and regional sea level rise on tidal dynamics in Pearl River Estuary
Authors: Li Xia , Cai Yanzi , Liu Zezheng , Mo Xiaobiao , Zhang Li , Zhang Cheng , Cui Baoshan , Ren Ze
Published: January 2023

Introduction

Recently, accelerated sea-level rise (SLR) has raised major concerns on estuarine management and restoration because it modifies estuarine hydrodynamics, such as tidal inundation extent and amplitude, tidal current asymmetry, flood frequency, etc. Understanding underlying processes which regulate estuarine tidal dynamics is critical for mitigating potential impacts on the coastal population and development.

Methods

We selected the Pearl River Estuary (PRE), an estuary with a higher regional SLR compared to the global SLR as the study area. To identify the effects of regional SLR on tidal dynamics, we analyzed long-term records of four tidal variables from 19 gauge stations between 1952 and 2020, including annual highest tidal levels (AHTLs), annual lowest tidal levels (ALTLs), annual mean tidal ranges (AMTRs), and annual mean tidal levels (AMTLs).

Results

Results suggested that variability in tidal variables was site-specific. The AMTRs decreased gradually from offshore regions to the upper reaches of rivers with a maximum at the mouth of the estuary. In contrast, the magnitudes of the AHTLs, AMTLs, and ALTLs decreased when approaching the coastline. Distance to the coastline had the highest correlations with the AHTLs, ALTLs, and AMTLs, followed by river width and river depth. The local SLR was responsible for the temporal variability in AHTLs, ALTLs, and AMTLs at the estuarine mouth with correlation coefficients from 0.43 to 0.85 (P < 0.001) but showed low correlations with these three tidal variables at the upper reaches of rivers (P > 0.001). Instead, the tidal variables were highly correlated with river discharge at the upper reaches of rivers, especially for the AHTLs (correlation coefficient = 0.83, P < 0.0001).

Conclusions

Our study demonstrated that the tidal dynamics demonstrate significant spatial-temporal variability. Geomorphology, river discharge, and sea levels have jointly affected estuarine hydrodynamics.
Comparative analysis of four types of mesoscale eddies in the North Pacific Subtropical Countercurrent region - part II seasonal variation
Authors: Sun Wenjin , An Mengxuan , Liu Jishan , Liu Jie , Yang Jingsong , Tan Wei , Sian Kenny T. C. Lim Kam , Ji Jinlin , Liu Yu , Dong Changming
Published: January 2023

The North Pacific Subtropical Countercurrent area (STCC) is high in mesoscale eddy activities. According to the rotation direction of the eddy flow field and the sign of temperature anomaly within the eddy, they can be divided into four categories: cyclonic cold-core eddy (CCE), anticyclonic warm-core eddy (AWE), cyclonic warm-core eddy (CWE) and anticyclonic cold-core eddy (ACE). CCE and AWE are called normal eddies, and CWE and ACE are named abnormal eddies. Based on the OFES data and vector geometry automatic detection method, we find that at the sea surface, the maximum monthly number of the CCE, AWE, CWE, and ACE occurs in December (765.70 ± 52.05), January (688.20 ± 82.53), August (373.40 ± 43.09) and August (533.00 ± 56.92), respectively. The number of normal eddies is more in winter and spring, and less in summer and autumn, while abnormal eddies have the opposite distribution. The maximum rotation velocity of the four types of eddies appears in June (11.71 ± 0.75 cm/s), June (12.24 ± 0.86 cm/s), May (10.63 ± 0.99 cm/s) and June (9.97 ± 0.91 cm/s), which is fast in winter and spring. The moving speed of the four types of eddies is almost similar (about 10 ~ 11 cm/s). The amplitude of normal and abnormal eddies is both high in summer and autumn, and low in winter and spring, with larger amplitudes in normal than abnormal eddies. The eccentricity (defined as the eccentricity of the ellipse obtained by fitting the eddy boundary) of the four types of eddies is also close to each other, and their variation ranges from 0.7 to 0.8, with no apparent seasonal variation. The vertical penetration depth, which has no significant seasonal difference, is 675.13 ± 67.50 m in cyclonic eddies (CCE and CWE), which is deeper than that 622.32 ± 81.85 m in anticyclonic eddies (ACE and AWE). In addition, increasing the defined temperature threshold for abnormal eddies can significantly reduce their numbers but does not change their seasonal variation trend.
Comparison of diagnostic accuracy for diabetes diagnosis: A systematic review and network meta-analysis
Authors: Duong Khanh N. C. , Tan Chia Jie , Rattanasiri Sasivimol , Thakkinstian Ammarin , Anothaisintawee Thunyarat , Chaiyakunapruk Nathorn
Published: January 2023

Aim

Fasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes.

Materials and methods

We performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed.

Results

Out of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR.

Conclusion

Our findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.
Caveolin-1 in vascular health and glaucoma: A critical vascular regulator and potential therapeutic target
Authors: Loo Jing Hong , Wang Zhaoran , Chong Rachel S.
Published: January 2023

Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found in most cell types. Cav-1 has been found to contribute significantly to ocular function, with mutations of Cav-1 being associated with a genetic risk of glaucoma development. Raised intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. Cav-1 may be involved in both IOP-dependent and independent mechanisms involving vascular dysregulation. Systemic vascular diseases including hypertension, diabetes and hyperlipidaemia, have been shown to be associated with glaucoma development. Cav-1 is closely interlinked with endothelial nitric oxide synthase pathways that mediate vascular function and prevent cardiovascular diseases. Endothelial nitric oxide synthase and endothelin-1 are key vasoactive molecules expressed in retinal blood vessels that function to autoregulate ocular blood flow (OBF). Disruptions in the homeostasis of OBF have led to a growing concept of impaired neurovascular coupling in glaucoma. The imbalance between perfusion and neuronal stimulation arising from Cav-1 depletion may result in relative ischemia of the optic nerve head and glaucomatous injury. OBF is also governed by circadian variation in IOP and systemic blood pressure (BP). Cav-1 has been shown to influence central BP variability and other circadian rhythms such as the diurnal phagolysosomal digestion of photoreceptor fragments and toxic substrates to maintain ocular health. Overall, the vast implications of Cav-1 on various ocular mechanisms leading to glaucoma suggest a potential for new therapeutics to enhance Cav-1 expression, which has seen success in other neurodegenerative diseases.
Effects of electroacupuncture on urinary metabolome and microbiota in presenilin1/2 conditional double knockout mice
Authors: Gao Jie , Zhou Nian , Lu Mengna , Wang Qixue , Zhao Chenyi , Wang Jian , Zhou Mingmei , Xu Ying
Published: January 2023

Aim

The treatment of Alzheimer’s disease (AD) is still a worldwide problem due to the unclear pathogenesis and lack of effective therapeutic targets. In recent years, metabolomic and gut microbiome changes in patients with AD have received increasing attention, and the microbiome–gut–brain (MGB) axis has been proposed as a new hypothesis for its etiology. Considering that electroacupuncture (EA) efficiently moderates cognitive deficits in AD and its mechanisms remain poorly understood, especially regarding its effects on the gut microbiota, we performed urinary metabolomic and microbial community profiling on EA-treated AD model mice, presenilin 1/2 conditional double knockout (PS cDKO) mice, to observe the effect of EA treatment on the gut microbiota in AD and find the connection between affected gut microbiota and metabolites.

Materials and methods

After 30 days of EA treatment, the recognition memory ability of PS cDKO mice was evaluated by the Y maze and the novel object recognition task. Urinary metabolomic profiling was conducted with the untargeted GC-MS method, and 16S rRNA sequence analysis was applied to analyze the microbial community. In addition, the association between differential urinary metabolites and gut microbiota was clarified by Spearman’s correlation coefficient analysis.

Key findings

In addition to reversed cognitive deficits, the urinary metabolome and gut microbiota of PS cDKO mice were altered as a result of EA treatment. Notably, the increased level of isovalerylglycine and the decreased levels of glycine and threonic acid in the urine of PS cDKO mice were reversed by EA treatment, which is involved in glyoxylate and dicarboxylate metabolism, as well as glycine, serine, and threonine metabolism. In addition to significantly enhancing the diversity and richness of the microbial community, EA treatment significantly increased the abundance of the genus Mucispirillum, while displaying no remarkable effect on the other major altered gut microbiota in PS cDKO mice, norank_f_Muribaculaceae, Lactobacillus, and Lachnospiraceae_NK4A136 group. There was a significant correlation between differential urinary metabolites and differential gut microbiota.

Significance

Electroacupuncture alleviates cognitive deficits in AD by modulating gut microbiota and metabolites. Mucispirillum might play an important role in the underlying mechanism of EA treatment. Our study provides a reference for future treatment of AD from the MGB axis.
Characterization of Klebsiella pneumoniae bacteriophages, KP1 and KP12, with deep learning-based structure prediction
Authors: Kim Youngju , Lee Sang-Mok , Nong Linh Khanh , Kim Jaehyung , Kim Seung Bum , Kim Donghyuk
Published: January 2023

Concerns over Klebsiella pneumoniae resistance to the last-line antibiotic treatment have prompted a reconsideration of bacteriophage therapy in public health. Biotechnological application of phages and their gene products as an alternative to antibiotics necessitates the understanding of their genomic context. This study sequenced, annotated, characterized, and compared two Klebsiella phages, KP1 and KP12. Physiological validations identified KP1 and KP12 as members of Myoviridae family. Both phages showed that their activities were stable in a wide range of pH and temperature. They exhibit a host specificity toward K. pneumoniae with a broad intraspecies host range. General features of genome size, coding density, percentage GC content, and phylogenetic analyses revealed that these bacteriophages are distantly related. Phage lytic proteins (endolysin, anti-/holin, spanin) identified by the local alignment against different databases, were subjected to further bioinformatic analyses including three-dimensional (3D) structure prediction by AlphaFold. AlphaFold models of phage lysis proteins were consistent with the published X-ray crystal structures, suggesting the presence of T4-like and P1/P2-like bacteriophage lysis proteins in KP1 and KP12, respectively. By providing the primary sequence information, this study contributes novel bacteriophages for research and development pipelines of phage therapy that ultimately, cater to the unmet clinical and industrial needs against K. pneumoniae pathogens.
Quinate-based ligands for irreversible inactivation of the bacterial virulence factor DHQ1 enzyme—A molecular insight†
Authors: Rodríguez Ángela , Maneiro María , Lence Emilio , Otero José M. , van Raaij Mark J. , Thompson Paul , Hawkins Alastair R. , González-Bello Concepción
Published: January 2023

Irreversible inhibition of the enzyme type I dehydroquinase (DHQ1), a promising target for anti-virulence drug development, has been explored by enhancing the electrophilicity of specific positions of the ligand towards covalent lysine modification. For ligand design, we made use of the advantages offered by the intrinsic acid-base properties of the amino substituents introduced in the quinate scaffold, namely compounds 6–7 (R configuration at C3), to generate a potential leaving group, as well as the recognition pattern of the enzyme. The reactivity of the C2–C3 bond (Re face) in the scaffold was also explored using compound 8. The results of the present study show that replacement of the C3 hydroxy group of (–)-quinic acid by a hydroxyamino substituent (compound 6) provides a time-dependent irreversible inhibitor, while compound 7, in which the latter functionality was substituted by an amino group, and the introduction of an oxirane ring at C2–C3 bond, compound 8, do not allow covalent modification of the enzyme. These outcomes were supported by resolution of the crystal structures of DHQ1 from Staphylococcus aureus (Sa-DHQ1) and Salmonella typhi (St-DHQ1) chemically modified by 6 at a resolution of 1.65 and 1.90 Å, respectively, and of St-DHQ1 in the complex with 8 (1.55 Å). The combination of these structural studies with extensive molecular dynamics simulation studies allowed us to understand the molecular basis of the type of inhibition observed. This study is a good example of the importance of achieving the correct geometry between the reactive center of the ligand (electrophile) and the enzyme nucleophile (lysine residue) to allow selective covalent modification. The outcomes obtained with the hydroxyamino derivative 6 also open up new possibilities in the design of irreversible inhibitors based on the use of amino substituents.
Purkinje-cell-specific DNA repair-deficient mice reveal that dietary restriction protects neurons by cell-intrinsic preservation of genomic health
Authors: Birkisdóttir María Björk , Van’t Sant Lisanne J. , Brandt Renata M. C. , Barnhoorn Sander , Hoeijmakers Jan H. J. , Vermeij Wilbert P. , Jaarsma Dick
Published: January 2023

Dietary restriction (DR) is a universal anti-aging intervention, which reduces age-related nervous system pathologies and neurological decline. The degree to which the neuroprotective effect of DR operates by attenuating cell intrinsic degradative processes rather than influencing non-cell autonomous factors such as glial and vascular health or systemic inflammatory status is incompletely understood. Following up on our finding that DR has a remarkably large beneficial effect on nervous system pathology in whole-body DNA repair-deficient progeroid mice, we show here that DR also exerts strong neuroprotection in mouse models in which a single neuronal cell type, i.e., cerebellar Purkinje cells, experience genotoxic stress and consequent premature aging-like dysfunction. Purkinje cell specific hypomorphic and knock-out ERCC1 mice on DR retained 40 and 25% more neurons, respectively, with equal protection against P53 activation, and alike results from whole-body ERCC1-deficient mice. Our findings show that DR strongly reduces Purkinje cell death in our Purkinje cell-specific accelerated aging mouse model, indicating that DR protects Purkinje cells from intrinsic DNA-damage-driven neurodegeneration.
Perspective insights into hydrogels and nanomaterials for ischemic stroke
Authors: Yu Qingbo , Jian Zhang , Yang Dan , Zhu Tao
Published: January 2023

Ischemic stroke (IS) is a neurological disorder prevalent worldwide with a high disability and mortality rate. In the clinic setting, tissue plasminogen activator (tPA) and thrombectomy could restore blood flow of the occlusion region and improve the outcomes of IS patients; however, these therapies are restricted by a narrow time window. Although several preclinical trials have revealed the molecular and cellular mechanisms underlying infarct lesions, the translatability of most findings is unsatisfactory, which contributes to the emergence of new biomaterials, such as hydrogels and nanomaterials, for the treatment of IS. Biomaterials function as structural scaffolds or are combined with other compounds to release therapeutic drugs. Biomaterial-mediated drug delivery approaches could optimize the therapeutic effects based on their brain-targeting property, biocompatibility, and functionality. This review summarizes the advances in biomaterials in the last several years, aiming to discuss the therapeutic potential of new biomaterials from the bench to bedside. The promising prospects of new biomaterials indicate the possibility of an organic combination between materialogy and medicine, which is a novel field under exploration.