Cryo-EM structure of the plant nitrate transporter AtCLCa reveals characteristics of the anion-binding site and the ATP-binding pocket.

Nitrate is one of the major nitrogen sources for most plants. Chloride channel (CLC) proteins mediate the transport and vacuole storage of nitrate in plants, but the structural basis of nitrate transport by plant CLC proteins remains unknown. Here, we solved the cryo-EM structure of ATP-bound Arabidopsis thaliana CLCa (AtCLCa) at 2.8 Å resolution. Structural comparison between nitrate-selective AtCLCa and chloride-selective CLC-7 reveals key differences in the central anion-binding site. We observed that the central nitrate is shifted by ∼1.4 Å from chloride, which is likely caused by a weaker interaction between the anion and Pro160; the side chains of aromatic residues around the central binding site are rearranged to accommodate the larger nitrate. Additionally, we identified the ATP-binding pocket of AtCLCa to be located between the cytosolic cystathionine ß-synthase domains and the N-terminus. The N-terminus may mediate the ATP inhibition of AtCLCa by interacting with both ATP and the pore-forming transmembrane helix. Together, our studies provide insights into the nitrate selectivity and ATP regulation of plant CLCs.

[Sequential mediating role of digital participation and health lifestyle in the relationship between socioeconomic status and depression of older adults].

OBJECTIVE: To explore the potential mechanisms of the relationship between socioeconomic status (SES) and depression of Chinese older adults through the mediating role of digital participation and health lifestyle. METHODS: Using the nationally representative data from the China Family Panel Studies in 2020, 4 846 participants aged 60 years and older were analyzed in our study. We explored the potential mechanisms of the relationship between SES and depression of Chinese older adults in the digital era through a chain multiple mediating effects model. The KHB (The Karlson, Holm, and Breen) method was used to analyze the mediating role of digital participation and health lifestyle and the proportion of mediating effect between the two was also calculated. A series of robustness tests were further conducted and the fit of the model was checked by structural equation modeling. RESULTS: The mean age of the 4 846 older adults included in this study was (68.20±5.07) years, 48.06% of whom were female and 51.94% were male. The KHB results showed that both digital participation and health lifestyle could mediate the relationship between SES and depression of older adults (P < 0.000 1) and the mediating role of health lifestyle accounted for a greater proportion than digital participation. And our study mainly found three potential pathways of SES and depression of older adults, including: (1) SES → digital participation → health lifestyle → depression, (2) SES → health lifestyle → depression, and (3) SES → depression. Structural equation modeling tests proved the overall fit of the model in this study. CONCLUSION: Our findings showed that in the digital age, in addition to the direct relationship between SES and depression of older adults, and the health lifestyle as a mediator between the relationship, there is also a sequential mediating role of digital participation and health lifestyle to reduce the risk of depression. The findings suggest that we should pay more attention to the probability of the digital divide exacerbating health inequalities and socioeconomic inequalities accumulation in the digital age and promote the co-progress of digital literacy and health literacy among older adults.

Impact of the COVID-19 pandemic on the hospital attendance of patients with primary cervical cancer in Heilongjiang, China.

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.

Discovery of novel benzimidazole derivatives as potent potassium-competitive acid blockers for the treatment of acid-related diseases.

H+, K+-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC50 = 9.32 µM) and A18 (IC50 = 5.83 µM) showed better inhibition at the enzyme level. In addition, gastric acid secretion inhibition was assessed in vivo, and the results showed that A12 and A18 significantly inhibited basal gastric acid secretion, 2-deoxy-d-glucose (2DG) stimulated gastric acid secretion and histamine-stimulated gastric acid secretion. In further in vitro metabolic experiments, A12 and A18 demonstrated excellent stability and low toxicity. Pharmacokinetic studies showed that the p.o. and i.v. half-lives of A18 were 3.21 h and 8.67 ± 1.15 h, respectively. In summary, A18 might be a novel and effective potassium-competitive acid blocker, and this study provides strong support for it use in the treatment of acid-related diseases.

Interface switch mediates signal transmission in a two-component system.

Two-component systems (TCS), which typically consist of a membrane-embedded histidine kinase and a cytoplasmic response regulator, are the dominant signaling proteins for transduction of environmental stimuli into cellular response pathways in prokaryotic cells. HptRSA is a recently identified TCS consisting of the G6P-associated sensor protein (HptA), transmembrane histidine kinase (HptS), and cytoplasmic effector (HptR). HptRSA mediates glucose-6-phosphate (G6P) uptake to support Staphylococcus aureus growth and multiplication within various host cells. How the mechanism by which HptRSA perceives G6P and triggers a downstream response has remained elusive. Here, we solved the HptA structures in apo and G6P-bound states. G6P binding in the cleft between two HptA domains caused a conformational closing movement. The solved structures of HptA in complex with the periplasmic domain of HptS showed that HptA interacts with HptS through both constitutive and switchable interfaces. The G6P-free form of HptA binds to the membrane-distal side of the HptS periplasmic domain (HptSp), resulting in a parallel conformation of the HptSp protomer pair. However, once HptA associates with G6P, its intramolecular domain closure switches the HptA-HptSp contact region into the membrane-proximal domain, which causes rotation and closure of the C termini of each HptSp protomer. Through biochemical and growth assays of HptA and HptS mutant variants, we proposed a distinct mechanism of interface switch-mediated signaling transduction. Our results provide mechanistic insights into bacterial nutrient sensing and expand our understanding of the activation modes by which TCS communicates external signals.

Exploring factors that influence the behavioural intention of medical students to use 3D gastroscopic model to learn how to operate gastroscope using UTAUT Model.

BACKGROUND: The application of virtual reality (VR) in gastroscopic operation teaching can be safe and effective, but the advantages can be realized only when students accept and use it. This study aims to identify the factors influencing Chinese clinical medical postgraduates on their intention to use the 3D gastroscopic model constructed based on VR technology using Unified Theory of Acceptance and Use of Technology (UTAUT) model. Students' demographic factors are also taken into consideration. METHODS: All methods were carried out in accordance with relevant guidelines. Data were collected from clinical medical postgraduates students in China using stratified sampling. A total of 292 questionnaires including valid responses were used in this study. Data were processed using Amos 24.0 and SPSS 26.0 software and the statistical analysis technique was based on structural equation modeling (SEM). RESULTS: The results showed that different from the mediator of home location and year of clinical learning, mediator of gender, university kind and graduate degree did not affect the behavioral intention. In addition, performance expectancy, facilitating condition, and social influence directly and indirectly have effect on behavioral intention. Also, the significance between social influence and performance expectancy, social influence and effort expectancy were verified. CONCLUSIONS: This study manifested that the proposed framework based on the UTAUT had explanatory power to identify the factors influencing the students' behavioral intention to use the 3D gastroscopic model constructed based on VR technology. Whereas, an important variable of effort expectancy in the frame of the SEM were not certified, thereby indicating that particular attention should be paid to this variable by universities and teachers before applying 3D gastroscopic model constructed based on VR technology in teaching. Added preparatory work is required such as explaining the basic knowledge of the operating steps of VR model and make students adequately understand its accessibility, which can probably improve the intentions of them to use it. The positive effects of social influence on performance expectancy and effort expectancy we proposed was also verified in this study, which provided a direction for future research.

Integrative Analysis of Metabolomic and Transcriptomic Data Reveals the Mechanism of Color Formation in Corms of Pinellia ternata.

Pinellia ternata (Thunb.) Breit. (P. ternata) is a very important plant that is commonly used in traditional Chinese medicine. Its corms can be used as medicine and function to alleviate cough, headache, and phlegm. The epidermis of P. ternata corms is often light yellow to yellow in color; however, within the range of P. ternata found in JingZhou City in Hubei Province, China, there is a form of P. ternata in which the epidermis of the corm is red. We found that the total flavonoid content of red P. ternata corms is significantly higher than that of yellow P. ternata corms. The objective of this study was to understand the molecular mechanisms behind the difference in epidermal color between the two forms of P. ternata. The results showed that a high content of anthocyanidin was responsible for the red epidermal color in P. ternata, and 15 metabolites, including cyanidin-3-O-rutinoside-5-O-glucoside, cyanidin-3-O-glucoside, and cyanidin-3-O-rutinoside, were screened as potential color markers in P. ternata through metabolomic analysis. Based on an analysis of the transcriptome, seven genes, including PtCHS1, PtCHS2, PtCHI1, PtDFR5, PtANS, PtUPD-GT2, and PtUPD-GT3, were found to have important effects on the biosynthesis of anthocyanins in the P. ternata corm epidermis. Furthermore, two transcription factors (TFs), bHLH1 and bHLH2, may have regulatory functions in the biosynthesis of anthocyanins in red P. ternata corms. Using an integrative analysis of the metabolomic and transcriptomic data, we identified five genes, PtCHI, PtDFR2, PtUPD-GT1, PtUPD-GT2, and PtUPD-GT3, that may play important roles in the presence of the red epidermis color in P. ternata corms.

Whole-plant microbiome profiling reveals a novel geminivirus associated with soybean stay-green disease.

Microbiota colonize every accessible plant tissue and play fundamental roles in plant growth and health. Soybean stay-green syndrome (SGS), a condition that causes delayed leaf senescence (stay-green), flat pods and abnormal seeds of soybean, has become the most serious disease of soybean in China. However, the direct cause of SGS is highly debated, and little is known about how SGS affect soybean microbiome dynamics, particularly the seed microbiome. We studied the bacterial, fungal, and viral communities associated with different soybean tissues with and without SGS using a multi-omics approach, and investigated the possible pathogenic agents associated with SGS and how SGS affects the assembly and functions of plant-associated microbiomes. We obtained a comprehensive view of the composition, function, loads, diversity, and dynamics of soybean microbiomes in the rhizosphere, root, stem, leaf, pod, and seed compartments, and discovered that soybean SGS was associated with dramatically increased microbial loads and dysbiosis of the bacterial microbiota in seeds. Furthermore, we identified a novel geminivirus that was strongly associated with soybean SGS, regardless of plant cultivar, sampling location, or harvest year. This whole-plant microbiome profiling of soybean provides the first demonstration of geminivirus infection associated with microbiota dysbiosis, which might represent a general microbiological symptom of plant diseases.

Conversion therapy, palliative chemotherapy and surgery, which of these is the best treatment for locally advanced and advanced pancreatic cancer?

A retrospective study was conducted to analyze which translational therapy, palliative chemotherapy and surgery is the best treatment for locally advanced and advanced pancreatic cancer, and to screen out the dominant population for the best treatment. A total of 83 patients with pancreatic cancer, including locally advanced and advanced pancreatic cancer, who had lost the opportunity for radical surgery and were admitted to Zhejiang Provincial People's Hospital between January 2015 and July 2021 were collected. A total of 39 patients received palliative chemotherapy, 25 patients received conversion therapy and 19 patients tried surgery at the first visit. We conducted survival follow-up and prognostic evaluation of 83 patients. The median overall survival (mOS) and median progression-free survival (mPFS) of 25 pancreatic cancer patients who received conversion therapy were longer than those of pancreatic cancer patients who received palliative chemotherapy (mOS: 16 months vs. 9 months, P = 0.001; mPFS: 11 months vs. 7.5 months, P = 0.038) and surgery (mOS: 16 months vs. 9 months, P = 0.018; mPFS: 11 months vs. 5.5 months, P < 0.001). Multivariate and Kaplan-Meier analysis showed that age, distant metastasis, and the degree of CA199 declined after chemotherapy were independent factors affecting overall survival (OS) of pancreatic cancer patients who received conversion therapy. Conversion therapy can improve OS and progression-free survival in patients with locally advanced or advanced pancreatic cancer to a certain extent. Some patients with advanced pancreatic cancer have surprising results after receiving conversion therapy.

Tumor-mutation burden as a marker for immunotherapy of pancreatic cancer: the case report and literature review.

Pancreatic cancer is digestive cancer with limited therapeutic options and a poor outcome. Pancreatic cancer has a high mortality rate, with a 5-year survival rate of less than 5%. The median survival after metastasis of the disease is less than 6 months. Studies have revealed that the standard treatment, including palliative chemotherapy or immunotherapy, is not significantly effective for pancreatic cancer. Herein, we report a case of pancreatic cancer who benefited from a combination of anti-PD-1 immunotherapy and chemotherapy.

Refractory hypokalemia caused by cetuximab with advanced colorectal cancer patients: the case series and literature review.

Cetuximab is the first-line treatment for advanced metastatic colon cancer. But cetuximab can cause electrolyte disturbances, including hypomagnesemia and hypokalemia. Among them, hypokalemia is often caused by hypomagnesemia, not directly caused by cetuximab. This article reports two cases of refractory hypokalemia caused by cetuximab without hypomagnesemia. The two patients had no abnormalities in serum potassium before cetuximab treatment. The occurrence of hypokalemia was clearly correlated with the cetuximab, and they were significantly improved after stopping or reducing the dose. At the same time, the appearance of hypokalemia is significantly related to the efficacy of cetuximab. They have received 37 and 35 cycles of cetuximab-related therapy, with condition stable periods of 12.8 and 15.1 months, respectively. Obviously, our report refutes the above view. In our opinion, hypokalemia, a side effect of cetuximab, may be directly caused by it, rather than secondary to hypomagnesemia. Similar to hypomagnesemia, the appearance of hypokalemia often indicates a better curative effect of cetuximab.

Spiromesifen contributes vascular developmental toxicity via disrupting endothelial cell proliferation and migration in zebrafish embryos.

Spiromesifen (SPF) is a specific contact pesticide, which has been widely used to control the growth of sucking insects like mites and whiteflies on crops. Although its residues in crops and effects on organisms has been extensively reported, its impact on the vasculature is still not being reported. In the present study, using human umbilical vein endothelial cells (HUVECs) and zebrafish embryos, we investigated the effects of SPF on blood vessel development and its mechanism of action. SPF exposure triggered abnormal blood vessel development, including vascular deletions and malformations, inhibition of CCV remodeling, and decrease of SIV areas. SPF exposure also obstructed the migration of endothelial cell from caudal hematopoietic tissue in zebrafish embryos. SPF damaged cytoskeleton, caused cell cycle arrest, inhibited the viability and migration of HUVECs. In addition, SPF also inhibited the expression of the VEGF/VEGFR pathway-related genes (hif1a, vegfa, flt1, and kdrl), cell cycle-related genes (ccnd1, ccne1, cdk2, and pcna), and Rho/ROCK pathway-related genes (itgb1, rho, rock, mlc-1, and vim-1). Taken together, SPF may inhibit the proliferation and migration of vascular endothelial cells through disturbing cytoskeleton via the Rho/ ROCK pathway, resulting in vascular malformation. Our study contributes to potential insight into the mechanism of SPF toxicity in angiocardiopathy.

Biochar affects methylmercury production and bioaccumulation in paddy soils: Insights from soil-derived dissolved organic matter.

Biochar has been used increasingly as a soil additive to control mercury (Hg) pollution in paddy rice fields. As the most active component of soil organic matter, soil dissolved organic matter (DOM) plays a vital role in the environmental fate of contaminants. However, there are very few studies to determine the impact of biochar on the Hg cycle in rice paddies using insights from DOM. This study used original and modified biochar to investigate their effect on DOM dynamics and their potential impact on methylmercury (MeHg) production and bioaccumulation in rice plants. Porewater DOM was collected to analyze the variations in soil-derived DOM in paddy soils. The results showed that the addition of biochar, whether in original or modified form, significantly reduced the bioaccumulation of MeHg in rice plants, especially in hulls and grains (p<0.05). However, MeHg production in soils was only inhibited by the modified biochar. Biochar addition induced a significant increase in DOM's aromaticity and molecular weight (p<0.05), which decreased Hg bioavailability. Furthermore, enhanced microbial activity was also observed in DOM (p<0.05), further increasing MeHg production in the soil. Thus, the effect of biochar on the fate of Hg cycle involves competition between the two different roles of DOM. This study identified a specific mechanism by which biochar affects Hg behavior in rice paddy soil and contributes to understanding the more general influence of biochar in agriculture and contaminant remediation.

Comparisons of Isolation Methods, Structural Features, and Bioactivities of the Polysaccharides from Three Common Panax Species: A Review of Recent Progress.

Panax spp. (Araliaceae family) are widely used medicinal plants and they mainly include Panax ginseng C.A. Meyer, Panax quinquefolium L. (American ginseng), and Panax notoginseng (notoginseng). Polysaccharides are the main active ingredients in these plants and have demonstrated diverse pharmacological functions, but comparisons of isolation methods, structural features, and bioactivities of these polysaccharides have not yet been reported. This review summarizes recent advances associated with 112 polysaccharides from ginseng, 25 polysaccharides from American ginseng, and 36 polysaccharides from notoginseng and it compares the differences in extraction, purification, structural features, and bioactivities. Most studies focus on ginseng polysaccharides and comparisons are typically made with the polysaccharides from American ginseng and notoginseng. For the extraction, purification, and structural analysis, the processes are similar for the polysaccharides from the three Panax species. Previous studies determined that 55 polysaccharides from ginseng, 18 polysaccharides from American ginseng, and 9 polysaccharides from notoginseng exhibited anti-tumor activity, immunoregulatory effects, anti-oxidant activity, and other pharmacological functions, which are mediated by multiple signaling pathways, including mitogen-activated protein kinase, nuclear factor kappa B, or redox balance pathways. This review can provide new insights into the similarities and differences among the polysaccharides from the three Panax species, which can facilitate and guide further studies to explore the medicinal properties of the Araliaceae family used in traditional Chinese medicine.

Phosphorylation of MtRopGEF2 by LYK3 mediates MtROP activity to regulate rhizobial infection in Medicago truncatula.

The formation of nitrogen-fixing no dules on legume roots requires the coordination of infection by rhizobia at the root epidermis with the initiation of cell divisions in the root cortex. During infection, rhizobia attach to the tip of elongating root hairs which then curl to entrap the rhizobia. However, the mechanism of root hair deformation and curling in response to symbiotic signals is still elusive. Here, we found that small GTPases (MtRac1/MtROP9 and its homologs) are required for root hair development and rhizobial infection in Medicago truncatula. Our results show that the Nod factor receptor LYK3 phosphorylates the guanine nucleotide exchange factor MtRopGEF2 at S73 which is critical for the polar growth of root hairs. In turn, phosphorylated MtRopGEF2 can activate MtRac1. Activated MtRac1 was found to localize at the tips of root hairs and to strongly interact with LYK3 and NFP. Taken together, our results support the hypothesis that MtRac1, LYK3, and NFP form a polarly localized receptor complex that regulates root hair deformation during rhizobial infection.

Triazine-cored polymeric vectors for antisense oligonucleotide delivery in vitro and in vivo.

BACKGROUND: The polymer-based drug/gene delivery is promising for the treatment of inherent or acquire disease, because of the polymer's structural flexibility, larger capacity for therapeutic agent, low host immunogenicity and less cost. Antisense therapy is an approach to fighting genetic disorders or infections using antisense oligonucleotides (AOs). Unfortunately, the naked AOs showed low therapeutic efficacy in vivo and in clinical trial due to their poor cellular uptake and fast clearance in bloodstream. In this study, a series of triazine-cored amphiphilic polymers (TAPs) were investigated for their potential to enhance delivery of AOs, 2'-O-methyl phosphorothioate RNA (2'-OMePS) and phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. RESULTS: TAPs significantly enhanced AO-induced exon-skipping in a GFP reporter-based myoblast and myotube culture system, and observed cytotoxicity of the TAPs were lower than Endoporter, Lipofectamine-2000 or PEI 25K. Application of optimized formulations of TAPs with AO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. The best ones for PMO and 2'-OMePS delivery have reached to 11-, 15-fold compared with the AO only in mdx mice, respectively. CONCLUSION: The study of triazine-cored amphiphilic polymers for AO delivery in vitro and in mdx mice indicated that the carrier's performances are related to the molecular size, compositions and hydrophilic-lipophilic balance (HLB) of the polymers, as well as the AO's structure. Improved exon-skipping efficiency of AOs observed in vitro and in mdx mice accompanied with low cytotoxicity demonstrated TAP polymers are potentials as safe and effective delivery carrier for gene/drug delivery.

A Rat Model of Polycystic Ovary Syndrome with Insulin Resistance Induced by Letrozole Combined with High Fat Diet.

BACKGROUND Clinically, most patients of polycystic ovary syndrome (PCOS) also have insulin resistance (IR). The methods for establishing PCOS-IR animal model include using dehydroepiandrosterone (DHEA) and sodium prasterone sulfate subcutaneous injection, testosterone propionate combined with high-fat diet, and so on. This study aimed to establish an animal model of PCOS-IR using letrozole combined with a high fat diet. MATERIAL AND METHODS Study rats received 0.5% carboxymethylcellulose solution (CMC) or letrozole solution (1 mg/kg/day), with normal diet as control group and a high fat diet as the model group, for 21, 24, 27, and 30 days. The body weight and length were measured weekly. On Day 22, 25, 28 and 31, the weight, and the short and long diameters of the rat ovaries were measured, and blood samples were collected for the measurement of fasting plasma glucose (FPG), fasting insulin (FINS), triglyceride (TG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T). Ovarian tissue was collected for paraffin sectioning and hematoxylin and eosin (H&E) staining. RESULTS In model groups, rats' weight was significantly increased (P<0.05). On Day 28 and 31, the weight, Lee's index, and ovarian volume significantly increased compared with Day 22 (P<0.05). There were more dense transparent saclike follicles on the ovary surface under the microscope in model groups. Levels of LH/FSH, T, and TG were substantially increased (P<0.05), but levels of FINS and HOMA-IR were significantly increased (P<0.05) on Day 28 and 31 in the model groups. CONCLUSIONS This study implied that letrozole combined with a high fat diet for 27 days could induce the PCOS-IR rat model which has the characteristics of ovarian polycystic changes and endocrine and metabolic disorders.

Optimization of the optical particle counter for online particle measurement in high-pressure gas.

With the aim to achieve fast and accurate online measurement of particle size and concentration in different high-pressure gas, the application of an optical particle counter (OPC) is extended from atmospheric pressure to high-pressure conditions (more than 2 MPa). But with the increase of the gas pressure, the performance of the OPC is reduced, resulting in the error of the tested particle size. In order to resolve this problem, an optimization model of optical window thickness is established for the optical sensor of the OPC based on the geometric optics theory. The effects of gas pressure, temperature, and medium on the optimized model are analyzed, which are helpful to improve the accuracy of the optical sensor. Finally, the feasibility, reliability, and accuracy of the method are verified through experiments.

Approach for correcting particle size distribution measured by optical particle counter in high-pressure gas pipes.

A set of online particle detection devices was developed for the quick and accurate assessment of particle size and concentration in high-pressure natural gas that can be applied at any pressure below 10 MPa. In actual site tests with P=3.42 and 2.36 MPa, the online tested results of particle size and concentration are generally smaller compared to those of the offline gathered under atmospheric conditions. That is mainly due to the detection performance degradation of an optical particle counter caused by gas pressure change leading to the refractive index change of the sounding medium with which the optical paths of the incident light and scattering light are altered. Aiming to solve this problem, an analysis of the dynamic change of optical measurement volume of the optical detection system with gas pressure was conducted based on the gas state parameters and geometric optics theory, and a dynamic model of both was established that can be accompanied by a particle size modification method based on light scattering theory. After a correction of tested results, the deviations in median diameter and concentration between the modified online and offline test results were within an acceptable range. Therefore, the proposed modification is a feasible and reliable approach to enhance online particle detection.

The crystal structure of the Hsp90 co-chaperone Cpr7 from Saccharomyces cerevisiae.

The versatility of Hsp90 can be attributed to the variety of co-chaperone proteins that modulate the role of Hsp90 in many cellular processes. As a co-chaperone of Hsp90, Cpr7 is essential for accelerating the cell growth in an Hsp90-containing trimeric complex. Here, we report the crystal structure of Cpr7 at a resolution of 1.8Å. It consists of an N-terminal PPI domain and a C-terminal TPR domain, and exhibits a U-shape conformation. Our studies revealed the aggregation state of Cpr7 in solution and the interaction properties between Cpr7 and the MEEVD sequence from the C-terminus of Hsp90. In addition, the structure and sequence analysis between Cpr7 and homologues revealed the structure basis both for the function differences between Cpr6 and Cpr7 and the functional complements between Cns1 and Cpr7. Our studies facilitate the understanding of Cpr7 and provide decent insights into the molecular mechanisms of the Hsp90 co-chaperone pathway.