基于农用地发展权的城乡建设用地价格衔接机制研究

本文采用条件价值评估法(CVM)对武汉市远城区农地发展权价值进行测算,并以此为基础,利用农地转换为最佳利用方式时的转换成本、农地农用价值估算农地合理价值,并分别与不同用途不同级别的城市建设用地基准地价进行对比衔接,建立城乡建设用地衔接机制。研究结果表明:武汉市农地发展权价值最小值分布在汉南区,为64.48元/m2,最大值在江夏区313.15元/m2;农地转换为最佳利用方式的合理价值为290.05~551.34元/m2;将各远城区农用地基准地价与城市商业用地、商务办公用地、住宅用地、工业用地基准地价级别分别进行衔接,其中东西湖区和江夏区对应基准地价级别较高,蔡甸区和黄陂区农用地基准地价所对应的级别处于中等,新洲区和汉南区最低。说明江夏区和东西湖区的经济较为发达,农民的思想比较活络,有较强的将农地转用的倾向,相应的汉南区由于社会经济水平较为落后,土地的开发压力和可能性都较小,因此农民将农地转用的倾向较为不明显,对于农地发展权的支付意愿也较低。基于发展权的城乡建设用地价格衔接机制的探索对农用地基准地价评估方法创新、征地补偿额制定、保证农民的权益和福祉具有重要的指导意义。

A multi-channel chemical sensor and its application in detecting hydrothermal vents

There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-channel chemical sensor to detect such anomalies which can be used in deep-sea at depths of more than 4 000 m. The design allowed five all-solid-state electrodes to be mounted on it and each (apart from one reference electrode) could be changed according to chemicals to be measured. Two experiments were conducted using the chemical sensors. The first was a shallow-sea trial which included sample measurements and in situ monitoring. pH, Eh, CO3^2- and SO4^2- electrodes were utilized to demonstrate that the chemical sensor was accurate and stable outside the laboratory. In the second experiment, the chemical sensor was integrated with pH, Eh, CO3^2- and H2S electrodes, and was used in 29 scans of the seabed along the Southwest Indian Ridge (SWIR) to detect hydrothermal vents, from which 27 sets of valid data were obtained. Hydrothermal vents were identified by analyzing the chemical anomalies, the primary judging criteria were decreasing voltages of Eh and H2S, matched by increasing voltages of pH and CO3^2- . We proposed that simultaneous detection of changes in these parameters will indicate a hydrothermal vent. Amongst the 27 valid sets of data, five potential hydrothermal vents were targeted using the proposed method. We suggest that our sensors could be widely employed by marine scientists.

Transition from minimal change disease to focal segmental glomerulosclerosis related to occupational exposure:A case report

BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.

View on the Clinical Value of QRS-T Angle

The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly dividedinto two types:plane angle and space angle.Studies show that the influence factors include two aspects of physiology and pathology of the angle,in pathological ways,the disease such as myocardial hypertrophy,myocardial ischemia,hypertension,ventricular arrhythmia has larger clinical significance.In recent years,the research on the risk stratification of the QRS-T angle on sudden death has made great progress,but there are still some disputes about whether the space angle can be replaced by the plane angle and the range of normal value and so on.

Engineering Rubisco to enhance CO_(2) utilization

Ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)is a pivotal enzyme that mediates the fixation of CO_(2).As the most abundant protein on earth,Rubisco has a significant impact on global carbon,water,and nitrogen cycles.However,the significantly low carboxylation activity and competing oxygenase activity of Rubisco greatly impede high carbon fixation efficiency.This review first summarizes the current efforts in directly or indirectly modifying plant Rubisco,which has been challenging due to its high conservation and limitations in chloroplast transformation techniques.However,recent advancements in understanding Rubisco biogenesis with the assistance of chaperones have enabled successful heterologous expression of all Rubisco forms,including plant Rubisco,in microorganisms.This breakthrough facilitates the acquisition and evaluation of modified proteins,streamlining the measurement of their activity.Moreover,the establishment of a screening system in E.coli opens up possibilities for obtaining high-performance mutant enzymes through directed evolution.Finally,this review emphasizes the utilization of Rubisco in microorganisms,not only expanding their carbon-fixing capabilities but also holding significant potential for enhancing biotransformation processes.

Waldenström macroglobulinemia:a challenging case treated with anti-CD19 CAR-T cell therapy

Waldenström macroglobulinemia(WM)is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M(IgM)protein(Owen et al.,2003).Common signs and symptoms include fatigue due to anemia,lymph node enlargement,hepatosplenomegaly,thrombocytopenia,symptoms related to high viscosity,and peripheral neuropathy,among others.Despite significant advances in WM treatment,this type of indolent lymphoma remains incurable,with a wide array of patient outcomes(Ruan et al.,2020).In recent years,chimeric antigen receptor T(CAR-T)cell therapy targeting cluster of differentiation 19(CD19)has shown unprecedented response rates and durability in the treatment of B-cell malignancies.In this report,we describe a challenging case of WM that involved multiple extramedullary sites,relapsed,and was refractory to chemotherapy,immunotherapy,and targeted therapy.After anti-CD19 CAR-T cell therapy,the tumor burden significantly decreased and the patient’s condition remained stable at the writing of this report.

A case of central nervous system infection with Scedosporium boydii

Scedosporium boydii is considered an opportunist fungal pathogen in immunocompromised patients.It also causes serious and fatal central nervous system infections.In this study,a man with brain abscesses infected with S.boydii was diagnosed using multiple methods,including microscopy,culture combined with Matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MOLDI-TOF MS),internal transcribed spacer sequencing and Metagenomic next-generation sequencing(mNGS).This successful diagnosis highlights the importance of using a variety of techniques to identify and treat infections caused by this dangerous fungus.

CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest

CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancers,such as acute promyelocytic leukemia and non-Hodgkin's lymphoma.However,no studies have yet investigated whether CUDC-101 is effective against myeloma.Herein,we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma(MM)cell lines and induces cell apoptosis in a time-and dose-dependent manner.Moreover,CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase(PI3K)and HDAC,and regulated the cell cycle G2/M arrest.Moreover,we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug.Bortezomib is one of the important drugs in MM treatment,and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib.The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade.Collectively,our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib,which provides insights into exploring new strategies for MM treatment.

基于个体化机器学习的原发性免疫性血小板减少症危重出血预测模型:一项全国前瞻性队列研究

原发性免疫性血小板减少症(ITP)中少见但至关重要的危重出血事件,给患者的预后、生活质量和治疗决策带来严重影响。尽管有一些研究探讨了ITP中与危重出血相关的风险因素,但目前尚缺乏大样本数据、大规模多中心研究结果以及针对ITP患者致命出血事件的预测模型。本研究首次采用国际血栓与止血学会新提出的ITP致命出血标准,利用大样本数据开发了首个基于机器学习的在线应用,用于预测ITP患者的致命出血.研究中,我们使用中国各地大型多中心数据进行开发,并对全国39家医疗中心进行为期一年的外部测试,得到了较好的训练、验证和测试数据集预测能力该基于新算法的便捷网络工具能够快速识别ITP患者的出血风险,辅助临床决策,有望未来降低不良事件的发生。

Development of an activity-directed selection system enabled significant improvement of the carboxylation efficiency of Rubisco

Photosynthetic CO2 fixation is the ultimate source of organic carbon on earth and thus is essential for crop production and carbon sequestration, Ribulose-1,5-bis- phosphate carboxylase/oxygenase （Rubisco） catalyzes the first step of photosynthetic CO2 fixation. However, the extreme low carboxylation efficiency of Rubisco makes it the most attractive target for improving pho- tosynthetic efficiency. Extensive studies have focused on re-engineering a more efficient enzyme, but the effort has been impeded by the limited understanding of its structure-function relationships and the lack of an effi- cient selection system towards its activity. To address the unsuccessful molecular engineering of Rubisco, we developed an Escherichia coil-based activity-directed selection system which links the growth of host cell solely to the Rubisco activity therein. A Synechococcus sp. PCC7002 Rubisco mutant with E49V and D82G sub- stitutions in the small subunit was selected from a total of 15,000 mutants by one round of evolution. This mutant showed an 85% increase in specific carboxyla- tion activity and a 45% improvement in catalytic efficiency towards CO2. The small-subunit E49V mutation was speculated to influence holoenzyme catalysis through interaction with the large-subunit Q225. This interaction is conserved among various Rubisco from higher plants and Chlamydomonas reinhardtii. Knowledge of these might provide clues for engineering Rubisco from higher plants, with the potential of increasing the crop yield.

Application of Proteomics in the Study of Tumor Metastasis

Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clini- cal management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental ap- proaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method- ologies will continue to extend its application in studying cancer metastasis.

Synthetic biology for CO2 fixation

Recycling of carbon dioxide(CO_2) into fuels and chemicals is a potential approach to reduce CO_2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimilate atmospheric CO_2 into organic compounds at ambient temperature and pressure. This provides a feasible way for biological production of fuels and chemicals from CO_2 under normal conditions. Recently great progress has been made in this research area, and dozens of CO_2-derived fuels and chemicals have been reported to be synthesized by autotrophic microbes. This is accompanied by investigations into natural CO_2-fixation pathways and the rapid development of new technologies in synthetic biology. This review first summarizes the six natural CO_2-fixation pathways reported to date, followed by an overview of recent progress in the design and engineering of CO_2-fixation pathways as well as energy supply patterns using the concept and tools of synthetic biology. Finally, we will discuss future prospects in biological fixation of CO_2.

Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma （MM）. While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 （Pirh2） in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor- kappaB （NF-κB） p65, pp65, plKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of plKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, plKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF- κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.

TLR4 inactivation protects from graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Graft-versus-host disease （GVHD） is the most common complication after hematopoietic stem cell transplantation. To clarify the role of Toll-like receptor 4 （TLR4）, which is a major receptor for bacterial lipopolysaccharides （LPS）, in the development of acute GVHD, we used a TLR4-knockout （TLR4-/-） mouse GVHD model and analyzed the underlying immunological mechanisms. When TLR4-/- mice were used as bone marrow and splenocyte cell graft donors or recipients, GVHD symptom occurrence and mortality were delayed compared to wild-type （TLR4＋/＋） mice. In addition, histopathological analyses revealed that in TLR4-/-→BALB/c chimeras, liver and small intestine tissue damage was reduced with minimal lymphocytic infiltration. In contrast to TLR4＋/＋, TLR4-/- mice dendritic cells did not express CD80, CD86, CD40, MHC-II or IL-12 during LPS induction and remained in an immature state. Furthermore, the ability of TLR4-/- mice spleen dendritic cells to promote allogeneic T-cell proliferation and, in particular, T-helper cell 1 （Th 1） development was obviously attenuated compared with TLR4＋/＋ mice dendritic cells, and the levels of interferon-T （IFN-γ） and IL-IO, Th2-cell specific cytokines, were significantly higher in the serum of TLR4-/-→BALB/c than in TLR4＋/＋→BALB/c chimeric mice. Overall, our data revealed that TLR4 may play a role in the pathogenesis of GVHD and that targeted TLR4 gene therapy might provide a new treatment approach to reduce the risk of GVHD.

Developing controllable hypermutable Clostridium cells through manipulating its methyl-directed mismatch repair system

Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial genus.Here we report a novel two-step strategy for de-veloping controllable hypermutable cells of Clostridium acetobutylicum,an important and representative indus-trial strain.Firstly,the mutS/L operon essential for methyl-directed mismatch repair(MMR)activity was inactivated from the genome of C.acetobutylicum to generate hy-permutable cells with over 250-fold increased mutation rates.Secondly,a proofreading control system carrying an inducibly expressed mutS/L operon was constructed.The hypermutable cells and the proofreading control system were integrated to form a controllable hypermut-able system SMBMutC,of which the mutation rates can be regulated by the concentration of anhydrotetracycline(aTc).Duplication of the miniPthl-tetR module of the proof-reading control system further signifi cantly expanded the regulatory space of the mutation rates,demonstrating hypermutable Clostridium cells with controllable mutation rates are generated.The developed C.acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress,indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.

How are MCPIP1 and cytokines mutually regulated in cancer-related immunity?

Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by multiple mechanisms at different levels,ranging from transcriptional to post-transcriptional and posttranslational processes.Monocyte chemoattractant protein-1 induced protein 1(MCPIP1),a potent immunosuppressive protein,was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1(MCP-1)and subsequently found to possess intrinsic RNase and deubiquitinase activities.MCPIP1 tightly regulates cytokines expression via various functions.Furthermore,cytokines such as interleukin 1 beta(IL-1B)and MCP-1 and inflammatory cytokines inducer lipopolysaccharide(LPS)strongly induce MCPIP1 expression.Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment.In this review,we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years

Invasive fungal infection （IFI） is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. We retrospectively reviewed the records of 408 patients un- dergoing alIo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 （22.5%） episodes suffered proven or probable IFI （4 patients were proven, 88 patients were probable）. Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen （HLA） mismatch, long-time neutropenia, and acute graft-versus-host-disease （GVHD） were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus （CMV） disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival （OS） rate for IFI was significantly lower than that of patients without IFI （41.9% vs. 63.6%, P〈0.01）.

High levels of serum IL-10 indicate disease progression,extramedullary involvement,and poor prognosis in multiple myeloma

Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.

Clinical characteristics and survival of patients with IgD multiple myeloma

MM(multiple myeloma)accounts for about 10%of hematological malignancies and 1%of cancer.IgD myeloma is a rare type of MM.It was reported that IgD type accounts for about 1%to 2%of all patients with MM abroad,while 3%to 8.9%in domestic cases.^(1) This immunoglobulin protein was first discovered by Dr.Rowe and Fahey in 1965.^(2) Half of a century had passed,the management of IgD MM remains a challenging field.

Review on the Urban Design and Planning for Jiangbei CBD in Chongqing

This paper briefly introduces the core concepts and major contents of the urban design and planning for the Jiangbei CBD in Chongqing. It presents some important methods and ideas for overall urban design from empirical perspectives, so as to provide certain references and experiences to similar urban design and planning projects.