The evolutionary arms race between transposable elements and piRNAs in Drosophila melanogaster.

BACKGROUND: The piwi-interacting RNAs (piRNAs) are small non-coding RNAs that specifically repress transposable elements (TEs) in the germline of Drosophila. Despite our expanding understanding of TE:piRNA interaction, whether there is an evolutionary arms race between TEs and piRNAs was unclear. RESULTS: Here, we studied the population genomics of TEs and piRNAs in the worldwide strains of D. melanogaster. By conducting a correlation analysis between TE contents and the abundance of piRNAs from ovaries of representative strains of D. melanogaster, we find positive correlations between TEs and piRNAs in six TE families. Our simulations further highlight that TE activities and the strength of purifying selection against TEs are important factors shaping the interactions between TEs and piRNAs. Our studies also suggest that the de novo generation of piRNAs is an important mechanism to repress the newly invaded TEs. CONCLUSIONS: Our results revealed the existence of an evolutionary arms race between the copy numbers of TEs and the abundance of antisense piRNAs at the population level. Although the interactions between TEs and piRNAs are complex and many factors should be considered to impact their interaction dynamics, our results suggest the emergence, repression specificity and strength of piRNAs on TEs should be considered in studying the landscapes of TE insertions in Drosophila. These results deepen our understanding of the interactions between piRNAs and TEs, and also provide novel insights into the nature of genomic conflicts of other forms.

Prelaryngeal and/or pretracheal lymph node metastasis could help to identify papillary thyroid carcinoma with intermediate risk from unilateral lobe cT1-2N0 papillary thyroid carcinoma.

Objective: The study aims to explore the possibility of prelaryngeal and/or pretracheal lymph node metastasis in identifying papillary thyroid carcinoma with more than 5 metastatic central lymph nodes from unilateral lobe cT1-2N0 papillary thyroid carcinoma. Methods: A retrospective analysis was conducted on patients who underwent the initial thyroid surgery for unilateral lobe cT1-2N0 PTC in a single tertiary center between July 2018 to December 2022. Multivariable binary logistic regression analysis was used to identify risk factors for unilateral lobe cT1-2N0 papillary thyroid carcinoma with more than 5 metastatic central lymph nodes. Results: A total of 737 patients were included in the study and 399 patients were confirmed to suffer from occult central lymph node metastasis. The larger size of the largest diameter of tumor (> 1cm; OR = 3.3, 95%CI 1.6 - 6.83; p = 0.001), pretracheal lymph node metastasis (OR = 5.91, 95%CI 2.73 - 12.77; p < 0.001), prelaryngeal lymph node metastasis (OR = 3.74, 95%CI 1.73 - 8.1; p = 0.001), ipsilateral paratracheal lymph node metastasis (OR = 12.22, 95%CI 3.43 - 43.48; p < 0.001), and contralateral paratracheal lymph node metastasis (OR = 7.68, 95%CI 3.86 - 15.3; p < 0.001) were confirmed to be risk factors for unilateral lobe cT1-2N0 PTC with more than 5 metastatic central lymph nodes. When more than two metastatic prelaryngeal and/or pretracheal lymph nodes occurred, the incidence of more than 5 metastatic central lymph nodes was 71.2%. Conclusion: Prelaryngeal and/or pretracheal lymph node metastasis could help to identify papillary thyroid carcinoma with more than 5 metastatic central lymph nodes from unilateral lobe cT1-2N0 papillary thyroid carcinoma. When more than two metastatic pretracheal and/or prelaryngeal lymph nodes occurred, total thyroidectomy and ipsilateral central lymph node dissection should be performed and contralateral paratracheal lymph node dissection might be also necessary.

The Aldose Reductase Inhibitor Epalrestat Maintains Blood-Brain Barrier Integrity by Enhancing Endothelial Cell Function during Cerebral Ischemia.

Excessive activation of aldose reductase (AR) in the brain is a risk factor for aggravating cerebral ischemia injury. Epalrestat is the only AR inhibitor with proven safety and efficacy, which is used in the clinical treatment of diabetic neuropathy. However, the molecular mechanisms underlying the neuroprotection of epalrestat remain unknown in the ischemic brain. Recent studies have found that blood-brain barrier (BBB) damage was mainly caused by increased apoptosis and autophagy of brain microvascular endothelial cells (BMVECs) and decreased expression of tight junction proteins. Thus, we hypothesized that the protective effect of epalrestat is mainly related to regulating the survival of BMVECs and tight junction protein levels after cerebral ischemia. To test this hypothesis, a mouse model of cerebral ischemia was established by permanent middle cerebral artery ligation (pMCAL), and the mice were treated with epalrestat or saline as a control. Epalrestat reduced the ischemic volume, enhanced BBB function, and improved the neurobehavior after cerebral ischemia. In vitro studies revealed that epalrestat increased the expression of tight junction proteins, and reduced the levels of cleaved-caspase3 and LC3 proteins in mouse BMVECs (bEnd.3 cells) exposed to oxygen-glucose deprivation (OGD). In addition, bicalutamide (an AKT inhibitor) and rapamycin (an mTOR inhibitor) increased the epalrestat-induced reduction in apoptosis and autophagy related protein levels in bEnd.3 cells with OGD treatment. Our findings suggest that epalrestat improves BBB function, which may be accomplished by reducing AR activation, promoting tight junction proteins expression, and upregulating AKT/mTOR signaling pathway to inhibit apoptosis and autophagy in BMVECs.

Relationship between pretracheal and/or prelaryngeal lymph node metastasis and paratracheal and lateral lymph node metastasis of papillary thyroid carcinoma: A meta-analysis.

Objective: We conducted a meta-analysis to study the relationship between pretracheal and/or prelaryngeal lymph node metastasis and paratracheal and lateral lymph node metastasis in papillary thyroid carcinoma. Method: A systematic literature search was conducted using PubMed, Embase, and the Cochrane Library electronic databases for studies published up to February 2022. The reference lists of retrieved articles were also reviewed. Two authors independently assessed the methodological quality and extracted the data. A random-effects model was used to calculate the overall pooled relative risk. Publication bias in these studies was evaluated using Egger's test and Begg's test. Results: Twenty-five independent studies involving 10,525 patients were included in the meta-analysis. The pooled relative risk for ipsilateral and contralateral paratracheal lymph node metastasis was 3.01 (95% confidence interval [CI]: 1.66, 5.45) and 5.68 (95% CI: 2.50, 12.88), respectively, in patients with pretracheal lymph node metastasis. Among patients with prelaryngeal lymph node metastasis, the pooled relative risk for ipsilateral paratracheal and/or pretracheal contralateral paratracheal, and lateral lymph node metastasis was 2.02 (95% CI: 1.90, 2.14), 2.22 (95% CI: 1.34, 3.67), and 3.85 (95% CI: 2.89, 5.14), respectively. Conclusion: Pretracheal lymph node metastasis and prelaryngeal lymph node metastasis were significantly associated with an increased likelihood of both ipsilateral lymph node metastasis and contralateral paratracheal lymph node metastasis in papillary thyroid carcinoma. Prelaryngeal lymph node metastasis was positively correlated with the incidence of lateral lymph node metastasis.

The Effect of Parathyroid Gland Autotransplantation on Hypoparathyroidism After Thyroid Surgery for Papillary Thyroid Carcinoma.

PURPOSE: There are some controversies over the relationship between parathyroid gland autotransplantation and permanent hypoparathyroidism. This study aimed to explore the relationship between parathyroid gland autotransplantation and postoperative hypoparathyroidism. PATIENTS AND METHODS: We performed a retrospective analysis of patients who underwent initial thyroid surgery for papillary thyroid carcinoma from January 2014 to December 2018. Patients were divided into 4 groups according to the number of autotransplanted parathyroid glands (group 1: 0 autotransplanted parathyroid gland, group 2: 1 autotransplanted parathyroid gland, group 3: 2 autotransplanted parathyroid glands, group 4: 3 autotransplanted parathyroid glands). Clinical data were analyzed among the four groups. RESULTS: The more parathyroid glands were transplanted, the higher the incidence of immediate hypoparathyroidism was (group 1: 32.9%, group 2: 52.9%, group 3: 65.8%, group 4: 82.4%; Pgroup 1 vs group 2 < 0.001, Pgroup 2 vs group 3 = 0.012, Pgroup 3 vs group 4 = 0.17). Parathyroid gland autotransplantation did not affect the incidence of permanent hypoparathyroidism (group 1: 1.4%, group 2: 1.3%, group 3: 0.9%, group 4: 0%; Pgroup 1 vs group 2 > 0.99, Pgroup 2 vs group 3 > 0.99, Pgroup 3 vs group 4 > 0.99). CONCLUSION: The number of autotransplanted parathyroid glands was positively associated with the incidence of postoperative immediate hypoparathyroidism. Parathyroid gland autotransplantation was not associated with permanent hypoparathyroidism.

The Accuracy of Near Infrared Autofluorescence in Identifying Parathyroid Gland During Thyroid and Parathyroid Surgery: A Meta-Analysis.

Objective: We aim to assess the accuracy of near infrared autofluorescence in identifying parathyroid gland during thyroid and parathyroid surgery. Method: A systematic literature search was conducted by using PubMed, Embase, and the Cochrane Library electronic databases for studies that were published up to February 2021. The reference lists of the retrieved articles were also reviewed. Two authors independently assessed the methodological quality and extracted the data. A random-effects model was used to calculate the combined variable. Publication bias in these studies was evaluated with the Deeks' funnel plots. Result: A total of 24 studies involving 2,062 patients and 6,680 specimens were included for the meta-analysis. The overall combined sensitivity and specificity, and the area under curve of near infrared autofluorescence were 0.96, 0.96, and 0.99, respectively. Significant heterogeneities were presented (Sen: I2 = 87.97%, Spe: I2 = 65.38%). In the subgroup of thyroid surgery, the combined sensitivity and specificity, and the area under curve of near infrared autofluorescence was 0.98, 0.99, and 0.99, respectively, and the heterogeneities were moderate (Sen: I2 = 59.71%, Spe: I2 = 67.65%). Conclusion: Near infrared autofluorescence is an excellent indicator for identifying parathyroid gland during thyroid and parathyroid surgery.

The Ability of Near-Infrared Autofluorescence to Protect Parathyroid Gland Function During Thyroid Surgery: A Meta-Analysis.

Objective: We conducted this meta-analysis to assess the ability of near-infrared autofluorescence to protect parathyroid gland function during thyroid surgery. Method: A systematic literature search was conducted using PubMed, Embase, and the Cochrane Library electronic databases for studies published up to February 2021. The reference lists of the retrieved articles were also reviewed. Two authors independently assessed methodological quality and extracted the data. A random-effects model was used to calculate the overall pooled variable and the weighted mean deviation. Publication bias in these studies was evaluated using the Egger's and Begg's tests. Result: Seven studies involving 1,480 patients were included in the analysis. Compared with patients in the naked eye group, the pooled relative risk of inadvertent parathyroid gland resection and parathyroid gland autotransplantation for the patients in the near-infrared autofluorescence group was 0.48 (95% CI, 0.26-0.9, p = 0.023) and 0.39 (95% CI, 0.09-1.68, p = 0.208), respectively. The pooled relative risk of hypocalcemia at 1 day postoperatively and at 6 months postoperatively for the patients in the near-infrared autofluorescence group was 0.49 (95% CI, 0.34-0.71, p < 0.001) and 0.34 (95% CI, 0.06-2.03, p = 0.238) compared with patients in the naked eye group. Conclusion: Near-infrared autofluorescence is significantly associated with a reduced risk of inadvertent parathyroid gland resection and hypocalcemia at 1 day postoperatively.

Evolutionary analysis and lineage designation of SARS-CoV-2 genomes.

The pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has caused immense global disruption. With the rapid accumulation of SARS-CoV-2 genome sequences, however, thousands of genomic variants of SARS-CoV-2 are now publicly available. To improve the tracing of the viral genomes' evolution during the development of the pandemic, we analyzed single nucleotide variants (SNVs) in 121,618 high-quality SARS-CoV-2 genomes. We divided these viral genomes into two major lineages (L and S) based on variants at sites 8782 and 28144, and further divided the L lineage into two major sublineages (L1 and L2) using SNVs at sites 3037, 14408, and 23403. Subsequently, we categorized them into 130 sublineages (37 in S, 35 in L1, and 58 in L2) based on marker SNVs at 201 additional genomic sites. This lineage/sublineage designation system has a hierarchical structure and reflects the relatedness among the subclades of the major lineages. We also provide a companion website (www.covid19evolution.net) that allows users to visualize sublineage information and upload their own SARS-CoV-2 genomes for sublineage classification. Finally, we discussed the possible roles of compensatory mutations and natural selection during SARS-CoV-2's evolution. These efforts will improve our understanding of the temporal and spatial dynamics of SARS-CoV-2's genome evolution.

The inferior parathyroid glands preserved in site recover faster than the superior parathyroid glands preserved in site after thyroid surgery for carcinoma.

Due to the great difficulty in being preserved in site for the variable positions, the inferior parathyroid glands were advised to being routinely autotransplanted to prevent permanent hypoparathyroidism. The aim of this study was to compare the performance in the function of the superior parathyroid glands preserved in site with that of the inferior parathyroid glands preserved in site.We conducted a retrospective study including patients who underwent thyroid surgery for papillary thyroid carcinoma at our department between January 2014 and June 2018. According to the number and original position of the autoplastic parathyroid gland(s), patients were divided into group 1 (1 superior parathyroid gland), group 2 (1 inferior parathyroid glands), group 3 (1 superior parathyroid gland and 1 inferior parathyroid gland) and group 4 (2 inferior parathyroid glands). The postoperative complications and serum parathyroid hormone and calcium were analyzed.A total of 368 patients were included in the study, among them 27, 243, 40, and 58 patients were divided into group 1, group 2, group 3, and group 4, respectively. Compared with those in group 2, the serum parathyroid hormones were higher at 1 week (2.98 ±â€Š1.52 vs 2.42 ±â€Š0.89, P = .049) and 2 weeks (3.49 ±â€Š1.42 vs 2.8 ±â€Š0.81, P = .019) postoperatively in group 1. There was also significantly different in the serum parathyroid hormone at 2 weeks postoperatively between group 3 and group 4 (2.95 ±â€Š0.98 vs 2.58 ±â€Š0.82, P = .047).The inferior parathyroid glands preserved in site recover faster than the superior parathyroid glands preserved in site.

On the origin and continuing evolution of SARS-CoV-2.

The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses had two major lineages (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. We found that L lineage was more prevalent than the S lineage within the limited patient samples we examined. The implication of these evolutionary changes on disease etiology remains unclear. These findings strongly underscores the urgent need for further comprehensive studies that combine viral genomic data, with epidemiological studies of coronavirus disease 2019 (COVID-19).

Technical Note: A new method to rapidly identify benign and malignant breast lumps through bioelectrical impedance spectroscopy.

PURPOSE: To evaluate the effectiveness of Bioelectrical Impedance Spectroscopy (BIS) in order to rapidly distinguish malignant vs benign breast masses. METHODS: A total of 622 breast masses from 489 patients were collected from January 2015 to June 2017. Every specimen was evaluated by a breast tissue bioimpedance analyzer (MScan1.0B) followed by morphological examination by pathologists. The results from BIS were compared with the morphological results from pathology (as a gold standard). The specificity and sensitivity of BIS were evaluated and the consistency test was performed. RESULTS: Compared with the pathology standard, BIS had good sensitivity (92.4%), specificity (96.0%), false positive rate (3.96%), and false negative rate (7.58%). The positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive values of BIS were 23.36, 0.0789, 73.49%, 99.07%, respectively. The kappa value of BIS was 0.794 ± 0.038 in the consistency test. CONCLUSION: Compared with the pathology standard, the BIS is an effective, convenient, and economical detection method to quickly differentiate benign and malignant breast masses with high accuracy. It may serve as a potential supplement of intraoperative pathological examinations.

[Influence of pyrrolidine dithiocarbamate (PDTC) on expression of transforming growth factor beta(1), matrix metalloproteinase-2 and tissue inhibitor-1 of metalloproteinase in rats with pulmonary damage induced by paraquat].

OBJECTIVE: To investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expression of transforming growth factor beta(1) (TGF-beta(1)), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ). METHODS: Fifty-four healthy male SD rats were randomly assigned into the control group (normal saline), the PQ-treatment groups (4 groups) and the PDTC treatment groups (4 groups). Except the rats in the control group, the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC (i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-beta(1) protein in the plasma, the mRNA expression of TGF-beta(1), MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope. RESULTS: The TGF-beta(1) protein, TGF-beta(1) and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P < 0.05 or P < 0.01), while the mRNA level of TIMP-1 was augmented continuously (P < 0.01) throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group, the TGF-beta(1) mRNA expression on the 3rd and the 14th day, 0.54 +/- 0.08 and 0.72 +/- 0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62 +/- 0.50 and 1.97 +/- 0.34 respective-ly, and the TIMP-1 mRNA on the 7th and 21st day, 1.79 +/- 0.21 and 2.00 +/- 0.34 respectively, were significantly decreased (P < 0.05 or P < 0.01). CONCLUSION: PDTC could attenuate paraquat-induced up-regulation of TGF-beta(1) and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjust-ing the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.

[Protective effects of vigabatrin and atropine against dimethoate induced-intoxication in mice].

OBJECTIVE: To investigate the protective effects of vigabatrin and atropine against the acute toxicity of dimethoate in male Kun-min mice. METHODS: The therapeutic schedules of vigabatrin (50 or 100 mg/kg) and (or) atropine (2.5 or 5.0 mg/kg) were performed according to the L(9) (3(4)) orthogonal test table. The survival time, the righting reflex and the onset of muscle fasciculations were observed after the administration of dimethoate. RESULTS: First, the main effects of vigabatrin, atropine and the interaction between them were statistically significant in the Univariate analysis of the survival time at the alpha level of 0.05 (F(V)= 4.73, P(V)= 0.015, F(A)= 50.88, P(A)= 0.000, F(VxA)= 4.17, P(VxA)= 0.007). The range of atropine was more than double of that of vigabatrin or their interaction (R(A)> 2RV or 2R(VxA)). So not only atropine and vigabatrin but also their combination interaction protected mice against dimethoate lethality. The atropine played the major role in diminishing the lethality induced by dimethoate. Second, only vigabatrin, while not atropine, delayed the mice from dimethoate-induced muscle fasciculation according its statistical results (F(V)= 6.87, P(V)= 0.003, F(A)= 0.03, P(A)= 0.968, F(VxA)= 1.134, P(VxA)= 0.356). It should be noted that vigabatrin could not completely prevent dimethoate induced-muscle fasciculation in the test. At last, both atropine and vigabatrin could maintain the righting reflex in the intoxication, however there was no interaction between them (F(V)= 5.81, P(V)= 0.006, F(A)= 9.05, P(A)= 0.001, F(VxA)= 1.34, P(VxA)= 0.257). CONCLUSION: Combined treatment with atropine and vigabatrin in the organophosphates intoxication seems reasonable and acceptable.

[Effects of 90-day oral dimethoate exposure on glutamatergic system and neurobehavioral performance in rats].

OBJECTIVE: To investigate the spatial learning and exploration along with the CNS excitatory amino acid neurotransmitters profiles in adult rats subchronically exposed to the anticholinesterase organophosphorus insecticide dimethoate. METHODS: Rats were gavaged daily with dimethoate (0, 5, 10 or 20 mg/kg via oral) in NS. for 90 days. Morris water maze tasks were used to test the spatial learning and memory in the rats after the dimethoate exposure. Simultaneously, rats were decapitated for the determination of brain cholinesterase AChE activities, glutamate concentrations, and the NMDA receptor NMDA-R densities and affinities in hippocampus. RESULTS: Latencies to find a hidden escape platform were significantly longer in dimethoate dosed groups than that of the control group in the place navigation tests. Subsequently, the times of crossing the location of platform which had been removed obviously decreased in the highest dose group compared with that of the control in the spatial probe tests (P < 0.05). AChE activity was significantly reduced 42% approximately 78% by all three doses of dimethoate (P < 0.05). Glutamate concentrations were increased significantly 132.9% approximately 134.5% by the two highest doses of dimethoate (P < 0.05). In addition, the NMDA receptor bindings were reduced 21.2% approximately 23.2% with the statistical significance at the same two highest doses (P < 0.05). Furthermore, the receptor affinities was reduced 33.1% by the highest dose group (P < 0.05). The lesions of spatial memory were statistically corrected with the decrease of the NMDA-R affinities (P < 0.05). CONCLUSION: The cholinergic lesion as well as the excitatory amino acid system alteration might attribute to the inferior ability in spatial learning and memory in dimethoate subchronically exposed rats.