Cholesterol-binding sequence is a key regulatory motif of cellular folding and conformational activation for C-reactive protein.

Human, rat, and mouse C-reactive protein (CRP) possess distinct expression patterns, but have similar conformations and conserved in vivo functions. We have previously demonstrated that this level-function mismatch is delicately tuned by the hidden activities of unfolded CRP. The cholesterol-binding sequence (CBS; a.a. 35-47) is a major functional motif exposed on monomeric CRP, which is the unfolded and activated conformation of CRP. We replaced the CBS of rat CRP with that of either mouse or human CRP, yielding two grafting mutants with unaffected pentameric assembly. However, these mutants exhibited altered cellular foldability and conformational activation efficiency that matched those of the CRP that provided the grafted CBS. These results indicate that CBS is a critical regulatory motif, whose variation maintains the pentameric assembly of CRP but derives distinct cellular foldabilities and conformational activation efficiencies, therefore helping to ensure that CRPs with various expression patterns exhibit overall conserved functions.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia.

BACKGROUND: The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mech anisms of lncRNAs in hP-MSC biology are unknown. AIM: To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology. METHODS: Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. RESULTS: We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription-polymerase chain reaction. SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins. CONCLUSION: Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

Improved sensitivity and positive predictive value of contrast-enhanced intraoperative ultrasound in colorectal cancer liver metastasis: a systematic review and meta-analysis.

Background: Surgery is an effective treatment for improving the survival rate of patients with colorectal cancer liver metastases (CRLM). However, accurately determining the resection margin of liver lesions during surgery remains challenging. Therefore, this study aimed to evaluate the sensitivity and predictive value of intraoperative contrast-enhanced ultrasound (CE-IOUS) in CRLM patients undergoing surgery. Methods: We performed a literature search of the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases using the following search terms: metastatic liver cancer, colorectal cancer, sensitivity, contrast-enhanced intraoperative ultrasound, CE-IOUS, colorectal liver metastases, and CRLM. The search period was set from the date of establishment of the database to September 2021. Quality assessment of diagnostic accuracy studies 2 (QUADAS-2) recommended by the Cochrane Collaboration was used to assess the methodological quality of the included studies, and network meta-analysis was performed using Stata 15.0 software. Results: A total of 10 articles met the inclusion criteria. The meta-analysis results showed that the overall sensitivity and specificity of CE-IOUS were 0.96 [95% confidence interval (CI), 0.95-0.97] and 0.75 (95% CI, 0.70-0.80), respectively. The overall sensitivity and specificity of IOUS were 0.84 (95% CI, 0.82-0.86) and 0.82 (95% CI, 0.77-0.87), respectively. The area under the summary receiving operating characteristic (SROC) curves (AUCs) of CE-IOUS and IOUS were 0.9753 and 0.8590, respectively. The odds ratio (OR) and 95% CI of CE-IOUS changed the surgical margin were 0.205 and 0.071-0.465, P=0.000, the difference was statistically significant. Discussion: Based on the results of this meta-analysis, CE-IOUS improved the sensitivity and predictive value of CRLM detection compared with IOUS, and is more suitable for intraoperative planning of surgical margins. At present, it is the most sensitive imaging method available, and is recommended for use during liver resection to provide doctors with more reliable information during surgery.

Celluar Folding Determinants and Conformational Plasticity of Native C-Reactive Protein.

C-reactive protein (CRP) is an acute phase reactant secreted by hepatocytes as a pentamer. The structure formation of pentameric CRP has been demonstrated to proceed in a stepwise manner in live cells. Here, we further dissect the sequence determinants that underlie the key steps in cellular folding and assembly of CRP. The initial folding of CRP subunits depends on a leading sequence with a conserved dipeptide that licenses the formation of the hydrophobic core. This drives the bonding of the intra-subunit disulfide requiring a favorable niche largely conferred by a single residue within the C-terminal helix. A conserved salt bridge then mediates the assembly of folded subunits into pentamer. The pentameric assembly harbors a pronounced plasticity in inter-subunit interactions, which may form the basis for a reversible activation of CRP in inflammation. These results provide insights into how sequence constraints are evolved to dictate structure and function of CRP.

Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women. METHODS: Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model. RESULTS: The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) -0.73 [-0.99, -0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) -0.65 [-0.92, -0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) -1.09 [-1.71, -0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women. CONCLUSIONS: Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.

Changes of semen quality in Chinese fertile men from 1985 to 2008 / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze the changes of semen quality in Chinese fertile men during the past 24 years.</p><p><b>METHODS</b>We reviewed the literature on the sperm quality of Chinese fertile males published from 1985 to 2008, collected relevant data, and analyzed the changes in semen volume, sperm density, and total sperm count by linear regression.</p><p><b>RESULTS</b>There were no significant changes either in semen volume during the period of 1985-2008 (P >0. 05) , or in sperm density and total sperm count from 1985 to 1994 (P > 0.05). However, significant decreases were observed during the latter 14 years in sperm density (from 81.5 x 10(6)/ml in 1995 to 66.7 x 10(6)/ml in 2008, with a mean annual reduction of 1.40%) and total sperm count (from 257.2 x 10(6) in 1995 to 185.9 x 10(6) in 2008, with a mean annual reduction of 2. 15%) (P < 0.05).</p><p><b>CONCLUSION</b>The semen quality of Chinese fertile men showed no significant changes from 1985 to 1995, but evidently declined from 1995 to 2008, which may be attributed to the aggravated environmental pollution induced by heavy chemical industry.</p>