Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

Objective After endoscopic resection of colorectal cancer with submucosal invasion(pT1 CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pT1 CRC,especially the effect of DSI on LNM.Methods Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results Twenty-eight of the 239 patients presented with LNM(11.7%),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1%(1/95),12.5%(7/56),and 48.8%(20/41),respectively.Conclusion Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.

Identification of quantitative trait loci for four morphologic traits under water stress in rice (Oryza sativa L.)

Late season drought coinciding with the rice booting to heading stage affects the development of plant height, panicle exserfion, and flag leaf size, and causes significant yield loss. In this study, a recombinant inbred line population derived from a cross between paddy and upland cultivars was used for data collection of the morphologic traits under well water and drought stress conditions. Drought stress was applied at the stage of panicle initiation in the field in 2002 and at the booting stage in PVC pipes in 2003. The data from stress conditions and their ratios （trait measured under stress condition/trait measured under well water condition） or differences （trait measured under stress condition minus trait measured under well water condition） were used for QTL analysis. Totally, 17 and 36 QTLs for these traits were identified in 2002 and 2003, respectively, which explained a range of 2.58%-29.82% of the phenotypic variation. Among them, six QTLs were commonly identified in the two years, suggesting that the drought stress in the two years was different. The genetic basis of these traits will provide useful information for improving rice late season drought resistance, and their application as indirect indices in rice late season drought resistance screening was also discussed.

Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

Bone marrow-derived mesenchymal stem cells(BMSCs)play a critical role in the osseointegration of bone and orthopedic implant.However,osseointegration between the Ti-based implants and the surrounding bone tissue must be improved due to titanium’s inherent defects.Surface modification stands out as a versatile technique to create instructive biomaterials that can actively direct stem cell fate.Here,we summarize the current approaches to promoting BMSC osteogenesis on the surface of titanium and its alloys.We will highlight the utilization of the unique properties of titanium and its alloys in promoting tissue regeneration,and discuss recent advances in understanding their role in regenerative medicine.We aim to provide a systematic and comprehensive review of approaches to promoting BMSC osteogenesis on the orthopedic implant surface.

Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.

大米中砷形态的快速测定使用HPLC/ICP-MS快速测定精白米中的五种砷形态

本文使用HPLC与ICP—MS联用对大米中有毒砷形态进行快速测定。该法分析速度快，可在4min内测定包括毒性相关无机形态As（Ⅲ）和As（Ⅴ）在内的5种砷形态，同时具有出色的灵敏度、准确度和精密度．

A four-band index for both liquid and solid water and its applications in the Aral Sea Basin

Various investigations have been conducted to analyze the water-coverage area of the Aral Sea and the Aral Sea Basin(ASB). However, the investigations incorporated considerable uncertainty and the used water indices had misclassification problem, which made different research groups present different results. Thus we first ascertain the boundaries of the ASB, the Syr and Amu river basins as well as their upper, middle and lower reaches. Then a four-band index for both liquid and solid water(ILSW) is proposed to address the misclassification problems of the classic water indices. ILSW is calculated by using the reflectance values of the green, red, near infrared, and thermal infrared bands, which combines the normalized difference water index(NDWI) and land surface temperature(LST) together. Validation results show that the ILSW water index has the highest accuracy by far in the Aral Sea Basin. Our results indicate that annual average decline of the water-coverage area was 963 km^(2) in the southern Aral Sea, whereas the northern Aral Sea has experienced little change. In the meanwhile, permanent ice and snow in upper reach of ASB has retreated considerably. Annual retreating rates of the permanent ice and snow were respectively 6233and 3841 km^(2) in upper reaches of Amu river basin(UARB) and Syr river basin(USRB). One of major reasons is that climate has become warmer in ASB. The climate change has caused serious water deficit problem. The water deficit had an increasing trend since the 1990s and its increasing rates was 3.778 billion m^(3) yearly on average. The total water deficit was 76.967 billion m^(3) on average in the whole area of ASB in the 2010s. However, up reaches of Syr river basin(USRB), a component area of ASB, had water surplus of 25.461 billion m^(3). These conclusions are useful for setting out a sustainable development strategy in ASB.

An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism.Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration.Therefore,designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge.Here,this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis,which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway.The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model.Furthermore,in an aged postmenopausal rat femoral condyle defect model,3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism,enabling personalized bone defect repair.These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Genome-wide Association Analysis of Ten Chilling Tolerance Indices at the Germination and Seedling Stages in Maize

Maize seedlings are very sensitive to chilling, especially during the transition phase from heterotrophic to autotrophic growth. Genetic dissection of the genetic basis of chilling tolerance would provide useful information for genetic improvement of maize inbreds. In this study, genome-wide association analysis was conducted to explore the genetic architecture of maize chilling tolerance at the seed germination and seedling stages with an association panel of 125 inbreds. Ten tolerance indices （ratios of the performance of 10 germination rates and seedling growth-related traits under chilling stress and control conditions） were investigated to assess the ability of chilling tolerance of the inbreds, and a total of 43 single nucleotide polymorphisms associated with chilling tolerance were detected, with none of them being related to chilling tolerance at both the germination and seedling stages simultaneously. Correlation analysis also revealed that the genetic basis of chilling tolerance at the seed germination stage is generally different from that at the seedling stage. In addition, a total of 40 candidate genes involving 31 of the 43 single nucleotide polymorphisms were predicted, and were grouped into five categories according to their functions. The possible roles of these candidate genes in chilling tolerance were also discussed.

Zinc alloy-based bone internal fixation screw with antibacterial and anti-osteolytic properties

There is no targeted effective treatment for patients undergoing internal fixation surgery/two-stage total joint revision surgery with a high risk of postoperative infection and osteolysis,while the rate of reoperation due to infection and osteolysis remains high.In this study,we report a pioneering application of implants made of biodegradable Zn-Ag alloy with active antibacterial and anti-osteolytic properties in three classical animal models,illustrating antibacterial,anti-osteolysis,and internal fixation for fractures.The antibacterial activity of the Zn-2Ag alloy was verified in a rat femur osteomyelitis prevention model,while the anti-osteolytic properties were evaluated using a mouse cranial osteolysis model.Moreover,the Zn-2Ag based screws showed similar performance in bone fracture fixation compared to the Ti-6Al-4V counterpart.The fracture healed completely after 3 months in the rabbit femoral condyle fracture model.Furthermore,the underlying antibacterial mechanism may include inhibition of biofilm formation,autolysis-related pathways,and antibiotic resistance pathways.Osseointegration mechanisms may include inhibition of osteoclast-associated protein expression,no effect on osteogenic protein expression,and no activation of related inflammatory protein expression.The empirical findings here reveal the great potential of Zn-Ag-based alloys for degradable biomaterials in internal fixation surgery/two-stage total joint revision surgery for patients with a high risk of postoperative infection and osteolysis.

The main restorer Rf3 of maize S type cytoplasmic male sterility encodes a PPR protein that functions in reduction of the transcripts of orf355

Dear Editor,Male sterile lines,especially cytoplasmic male sterile(CMS)lines,are extensively used in commercial hybrid seed production.Therefore a better understanding of the genetic basis of fertility restoration for CMS is important for the utility of heterosis in crops.In general,restorer of fertility(Rf)is controlled by one or two major genomic genes,and most of the Rf genes encode pro-teins containing P type pentatricopeptide repeat(PPR)motifs(Wang et al.,2006;Hu et al.,2012;Tang et al.,2014;Liu et al.,2016).S type CMS(CMS-S)is the main type of maize CMS with wide cytoplasmic sources,and orf355-orf77 in CMS-S was associated with male sterility(Zabala et al.,1997).The 5'stem-loop of the transcript of orf355-orf77 was thought to be associ-ated with its stability(Xiao et al.,2006).Recently,Xiao et al.(2020)confirmed that orf355 is the causal gene of CMS-S.Rf3,the main restorer of CMS-S,has been mapped to the long arm of chromosome 2 for a long time(Laughnan and Gabay,1978).Since then,great efforts have been made on genetic mapping and cloning of this gene(Xu et al.,2009).

Genome-wide identification, evolution, and expression analysis of RNA-binding glycine-rich protein family in maize

The RNA‐binding glycine‐rich protein（RB‐GRP）family is characterized by the presence of a glycine‐rich domain arranged in（Gly）n‐X repeats and an RNA‐recognition motif（RRM）. RB‐GRPs participate in varied physiological and biochemical processes especially in the stress response of plants. In this study, a total of 23 RB‐GRPs distributed on 10 chromosomes were identified in maize（Zea mays L.）, and they were divided into four subgroups according to their conserved domain architecture. Five pairs of paralogs were identified,while none of them was located on the same chromosomal region, suggesting that segmental duplication is predominant in the duplication events of the RB‐GRPs in maize. Comparative analysis of RB‐GRPs in maize, Arabidopsis（Arabidopsis thaliana L.）, rice（Oryza sativa L.）, and wheat（Triticum aestivum）revealed that two exclusive subgroups were only identified in maize. Expression of eight ZmRB‐GRPs was significantly regulated by at least two kinds of stresses. In addition, cis‐elements predicted in the promoter regions of the ZmRB‐GRPs also indicated that these ZmRB‐GRPs would be involved in stress response of maize. The preliminary genome‐wide analysis of the RB‐GRPs in maize would provide useful information for further study on the function of the ZmRB‐GRPs.

Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection

Orthopedic implants account for 99%of orthopedic surgeries,however,orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality.Current antibiotic treatments still lack the capacity to target bone infection sites,thereby resulting in unsatisfactory therapeutic effects.Here,the bone infection site targeting efficacy of D6 and UBI29-41 peptides was investigated,and bone-and-bacteria dual-targeted nanoparticles(NPs)with D6 and UBI29-41 peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site.The results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy,excellent biocompatibility and effective antibacterial properties in vitro.Furthermore,in a rat model of orthopedic implant-related infection with methicillin-resistant Staphylococcus aureus,the growth of bacteria was evidently inhibited without cytotoxicity,thus realizing the early treatment of implant-related infection.Hence,the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.

Hydrolysis of polyaluminum chloride prior to coagulation:Effects on coagulation behavior and implications for improving coagulation performance

The effects of polyaluminum chloride（PACl） hydrolysis prior to coagulation on both the coagulation zone and coagulation performance of a kaolin suspension were investigated by a novel jar test named the ＂reversed coagulation test＂.The tests showed that PACl hydrolysis prior to coagulation decreased the performance of charge neutralization coagulation in the case of short-time slow mixing（10 min;G = 15 sec-1） and increased the optimal dosage for charge neutralization and sweep coagulation.Moreover,the hydrolysis time had insignificant effects on the size and zeta potential of PACl precipitates and the residual turbidity of the raw water.However,PACl hydrolysis prior to coagulation and the size of PACl precipitates had a negligible effect on the performance of sweep coagulation.The results imply that,in practice,preparing a PACl solution with deionized water,rather than tap water or the outlet water from a wastewater treatment unit,can significantly save PACl consumption and improve the performance of charge neutralization coagulation,while preparing the PACl solution with tap or outlet water would not affect the performance of sweep coagulation.In addition,the optimal rapid mixing intensity appears to be determined by a balance between the degree of coagulant hydrolysis before contacting the primary particles and the average size of flocs in the rapid mixing period.These results provide new insights into the role of PACl hydrolysis and will be useful for improving coagulation efficiency.

Immunomodulatory biomaterials against bacterial infections:Progress,challenges,and future perspectives

Bacterial infectious diseases are one of the leading causes of death worldwide.Even with the use of multiple antibiotic treatment strategies,4.95 million people died from drug-resistant bacterial infections in 2019.By 2050,the number of deaths will reach 10 milion annually.The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants.In addition,the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the longterm treatment of chronic bacterial infections.The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells.Therefore,there is an urgent need for effective alternatives to treat bacterial infections.Accordingly,the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest;however,a comprehensive review of their research progress is lacking.In this review,we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection.First,we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections.Then,we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages.Moreover,we discuss biomaterial-mediated bacterial vaccines'potential applications and challenges for activating innate and adaptive immune memory.This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

Felodipine enhances aminoglycosides efficacy against implant infections caused by methicillin-resistant Staphylococcus aureus,persisters and biofilms

Methicillin-resistant Staphylococcus aureus(MRSA),biofilms,and persisters are three major factors leading to recurrent and recalcitrant implant infections.Although antibiotics are still the primary treatment for chronic implant infections in clinical,only few drugs are effective in clearing persisters and formed biofilms.Here,felodipine,a dihydropyridine calcium channel blocker,was reported for the first time to have antibacterial effects against MRSA,biofilm,and persisters.Even after continuous exposure to sub-lethal concentrations of felodipine,bacteria are less likely to develop resistance.Besides,low doses of felodipine enhances the antibacterial activity of gentamicin by inhibiting the expression of protein associated with aminoglycoside resistance(aacA-aphD).Next,biofilm eradication test and persisters killing assay suggested felodipine has an excellent bactericidal effect against formed biofilms and persisters.Furthermore,the result of protein profiling,and quantitative metabonomics analysis indicated felodipine reduce MRSA virulence(agrABC),biofilm formation and TCA cycle.Then,molecular docking showed felodipine inhibit the growth of persisters by binding to the H pocket of ClpP protease,which could lead to substantial protein degradation.Furthermore,murine infection models suggested felodipine in combination with gentamicin alleviate bacterial burden and inflammatory response.In conclusion,low dose of felodipine might be a promising agent for biomaterial delivery to enhance aminoglycosides efficacy against implant infections caused by MRSA,biofilm,and persisters.

Human exposure to a mixture of endocrine disruptors and serum levels of thyroid hormones:A cross-sectional study

Exposure to endocrine disruptors(EDCs) could disrupt thyroid hormone homeostasis. However, human epidemiological studies reported inconsistent observations, and scarce information on the effect of a mixture of chemicals. The aim of the present study was to examine the associations of multiple chemicals with thyroid hormones among adults from China. We measured serum levels of thyroid hormones and urinary levels of 11 EDCs, including six phthalate metabolites, bisphenol A(BPA), bisphenol F(BPF), bisphenol S(BPS), perchlorate, and thiocyanate among 177 healthy adults without occupational exposure. Associations of multiple urinary analytes with serum thyroid hormones were examined by performing general linear regression analysis and bayesian kernal machine regression analysis. These EDCs were detected in almost all samples. After adjusting for various covariates, we observed only BPF significantly associated with total thyroxin(TT4)(β=-0.27, 95% confidence interval(CI) [-0.41,-0.14]), total triiodothyronine(TT3)(β=-0.02 95% CI [-0.03,-0.01]), free T4(fT4)(β=-0.02, 95% CI [-0.03,-0.01]), and free T3(fT3)(β=-0.04, 95% CI [-0.07,-0.01]), and mono-(2-ethyl-5-oxohexyl) phthalate(MEOHP) and monoethyl phthalate(MEP) positively associated with TT4(β=0.24, 95% CI [0.01, 0.48]) and fT4(β=0.02, 95% CI [0.01, 0.04]), respectively. Moreover, we observed significant dose-response relationships between TT4 and the mixture of11 EDCs, and BPF was the main contributor to the mixture effect, suggesting the priority of potential effect of BPF on disrupting thyroid function under a real scenario of human exposure to multiple EDCs. Our findings supported the hypothesis that human exposure to low levels of EDCs could alter thyroid hormones homeostasis among non-occupational healthy adults.