Targeting Sex Determination to Suppress Mosquito Populations.

Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insuficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.

Exosomal miRNA in early-stage hepatocellular carcinoma.

The incidence and mortality of hepatic carcinoma (HCC) remain high, and early diagnosis of HCC is seen as a key approach in improving clinical outcomes. However, the sensitivity and specificity of current early screening methods for HCC are not satisfactory. In recent years, research around exosomal miRNA has gradually increased, and these molecules have emerged as attractive candidates for early diagnosis and treatment of HCC. This review summarizes the feasibility of using miRNAs in peripheral blood exosomes as early diagnostic tools for HCC.

Serotonin Signals Overcome Loser Mentality in Drosophila.

Traumatic experiences generate stressful neurological effects in the exposed persons and animals. Previous studies have demonstrated that in many species, including Drosophila, the defeated animal has a higher probability of losing subsequent fights. However, the neural basis of this "loser effect" is largely unknown. We herein report that elevated serotonin (5-HT) signaling helps a loser to overcome suppressive neurological states. Coerced activation of 5-HT neurons increases aggression in males and promotes losers to both vigorously re-engage in fights and even defeat the previous winners and regain mating motivation. P1 neurons act upstream and 5-HT1B neurons in the ellipsoid body act downstream of 5-HT neurons to arouse losers. Our results demonstrate an ancient neural mechanism of regulating depressive behavioral states after distressing events.

The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the most common degenerative disease all over the word. Our previous study confirmed that the downregulated circ-GRB10 directly interacts with miR-328-5p, which modulate ERBB2 and leads to the degeneration of intervertebral disc; however, the underpinning mechanism of circ-GRB10 dysregulation remains unclear. We identified that FUS and demonstrated that circ-GBR10 biosynthesis in nucleus pulposus (NP) cells was promoted by FUS, whose expression was controlled by miR-141-3p. In addition, ERBB2 downregulation led to decreased Erk1/2 phosphorylation which enhanced miR-141-3p production in NP cells. In vivo data indicated that circ-GRB10 inhibited IDD in rat model. The present study revealed that miR-141-3p and FUS are key factors that regulate circ-GRB10 synthesis in NP cells. In addition, circ-GBR10 participates in the molecular circuitry that controls human IDD development. These findings provide a basis for further functional, diagnostic and therapeutic studies of circ-GRB10 in IDD.

Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR­185­5p and matrix metalloproteinase 2.

Intervertebral disc degeneration (IDD) is an important cause of lower back pain, although the underlying mechanisms remain poorly understood. The present study aimed to examine the role of a circular RNA derived from tissue inhibitor of metallopeptidases 2 (circ­TIMP2) in degenerative nucleus pulposus (NP) tissues, and to validate its function in cultured human NP cells. Overexpression of miR­185­5p in NP cells markedly inhibited the enhanced extracellular matrix (ECM) catabolism induced by tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß) treatment. Bioinformatics analysis demonstrated that matrix metalloproteinase 2 (MMP2) was a potential target of miR­185­5p. MMP2 protein expression levels were increased following treatment with TNF­α and IL­1ß in NP cells compared with those in untreated cells, and this effect was attenuated by transfection with miR­185­5p. Compared with normal NP tissues, IDD samples exhibited higher circ­TIMP2 expression levels. In addition, overexpression of circ­TIMP2 promoted ECM catabolism and suppressed ECM anabolism. Furthermore, circ­TIMP2 sequestered miR­185­5p, which may potentially upregulate the target genes associated with ECM degradation. In conclusion, the results of the present study revealed that circ­TIMP2 promoted TNF­α­ and IL­1ß­induced NP cell imbalance between ECM anabolism and catabolism via miR­185­5p­MMP2 signaling. These findings provide a potential therapeutic option for the treatment of IDD.

The circular RNA FAM169A functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-583 and BTRC.

Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, although the underlying mechanisms remain poorly understood. In this study we examined the role of circular RNA FAM169A (circ-FAM169A) in degenerative nucleus pulposus (NP) tissues, and validated its function in cultured human NP cells. Overexpression of circ-FAM169A in NP cells markedly enhanced extracellular matrix (ECM) catabolism and suppressed ECM anabolism in NP cells. Furthermore, circ-FAM169A sequestered miR-583, which could potentially upregulate BTRC, an inducer of the NF-κB signaling pathway. In conclusion, the present study revealed that circ-FAM169A promotes IDD development via miR-583/BTRC signaling. These findings provide a potential therapeutic option for the treatment of IDD.

Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk.

Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the underlying mechanisms remain poorly understood. Compared with normal nucleus pulposus (NP) tissues, the expression of circ-GRB10 was downregulated in IDD. Furthermore, overexpression of circ-GRB10 inhibited NP cell apoptosis. circ-GRB10 could sequester miR-328-5p, which could potentially lead to the upregulation of target genes related to cell proliferation via the ErbB pathway. In conclusion, the present study revealed that circ-GRB10/miR-328-5p/ERBB2 signaling pathway is involved in IDD development, suggesting that circ-GRB10 might be a novel therapeutic target for IDD.

Analysis of the typical clinical features of posterior cruciate ligament rupture and comparison of arthroscopic surgery and conservative treatment / 中国内镜杂志

Objective To observe the clinical features of posterior cruciate ligament rupture and compare the efficacy of arthroscopic surgery and conservative treatment. Methods 128 patients, including 63 patients treated by arthroscopic surgery and 65 patients treated by conservative operation were included in the study. Statistical analysis was performed using SPSS 17.0 statistical software package. Results In the present study, after 24 month follow up, the PDT grade in the arthroscopic surgery group was better than that in conservative treatment group. The Lysol score in the arthroscopic surgery group was significantly higher that observed in the conservative treatment group (P < 0.05). There was no significantly difference for the Tiger score between the arthroscopic surgery group and conservative treatment group. Conclusion Arthroscopic treatment of posterior curiae ligament rupture is more effective than conservative treatment, especially in the treatment of joint stability and so on.

Taotie neurons regulate appetite in Drosophila.

The brain has an essential role in maintaining a balance between energy intake and expenditure of the body. Deciphering the processes underlying the decision-making for timely feeding of appropriate amounts may improve our understanding of physiological and psychological disorders related to feeding control. Here, we identify a group of appetite-enhancing neurons in a behavioural screen for flies with increased appetite. Manipulating the activity of these neurons, which we name Taotie neurons, induces bidirectional changes in feeding motivation. Long-term stimulation of Taotie neurons results in flies with highly obese phenotypes. Furthermore, we show that the in vivo activity of Taotie neurons in the neuroendocrine region reflects the hunger/satiety states of un-manipulated animals, and that appetitive-enhancing Taotie neurons control the secretion of insulin, a known regulator of feeding behaviour. Thus, our study reveals a new set of neurons regulating feeding behaviour in the high brain regions that represents physiological hunger states and control feeding behaviour in Drosophila.

Structure of the GTP Form of Elongation Factor 4 (EF4) Bound to the Ribosome.

Elongation factor 4 (EF4) is a member of the family of ribosome-dependent translational GTPase factors, along with elongation factor G and BPI-inducible protein A. Although EF4 is highly conserved in bacterial, mitochondrial, and chloroplast genomes, its exact biological function remains controversial. Here we present the cryo-EM reconstitution of the GTP form of EF4 bound to the ribosome with P and E site tRNAs at 3.8-Å resolution. Interestingly, our structure reveals an unrotated ribosome rather than a clockwise-rotated ribosome, as observed in the presence of EF4-GDP and P site tRNA. In addition, we also observed a counterclockwise-rotated form of the above complex at 5.7-Å resolution. Taken together, our results shed light on the interactions formed between EF4, the ribosome, and the P site tRNA and illuminate the GTPase activation mechanism at previously unresolved detail.

Downregulation of miR-27b is Involved in Loss of Type II Collagen by Directly Targeting Matrix Metalloproteinase 13 (MMP13) in Human Intervertebral Disc Degeneration.

STUDY DESIGN: A microRNA (miRNA) study. OBJECTIVE: The purpose of this study was to identify intervertebral disc degeneration (IDD)-specific miRNAs, followed by functional validation of results. SUMMARY OF BACKGROUND DATA: IDD is the major contributor to back radicular pain, and the molecular mechanisms underlying this disease are not completely understood. Accumulating evidence suggests that miRNAs play an important role in IDD, but the role of specific miRNAs involved in this disease remains elusive. METHODS: An initial screening of nucleus pulposus (NP) tissues, miRNA expression by miRNA microarray, was performed using samples from 10 patients with degenerative disc disease and 10 patients with lumbar fracture (as controls). Subsequently, differential expression was validated using quantitative reverse transcriptase PCR (qRT-PCR). The level of differentially expressed miRNAs in degenerative NP tissues was investigated, and then functional analysis of the miRNAs in regulating collagen II expression was carried out. Western blotting and luciferase reporter assays were also used to detect the target gene. RESULTS: We identified 23 miRNAs that were differentially expressed (16 upregulated and 7 downregulated) in patients compared with controls. After qRT-PCR confirmation, miR-27b was significantly downregulated in degenerative NP tissues when compared with controls. Moreover, its level was correlated with grade of disc degeneration. Overexpression of miR-27b promoted type II collagen expression in NP cells. Bioinformatics target prediction identified matrix metalloproteinase 13 (MMP13) as a putative target of miR-27b. Futhermore, luciferase reporter assays demonstrated that miR-27b directly targets MMP13 and affects the protein expression of MMP13 in NP cells. Expression of MMP13 negatively correlated with miR-27b expression in degenerative NP tissues. CONCLUSION: The downregulation of miR-27b induces type II collagen loss by directly targeting MMP13, leading to the development of IDD. Our study also underscores the potential of miR-27b as a novel therapeutic target in human IDD. LEVEL OF EVIDENCE: 3.

[Changes of Serum Gonadal Hormones Levels During Musk-secreting Period and Estrus of Moschus berezovskii].

OBJECTIVE: To detect concentrations of serum gonadal hormones (testosterone, estradiol and progesterone) in musk-secreting period and estrus of Moschus berezovskii, and to study the association of serum gonadal hormones concentrations and musk-secreting. METHODS: The concentrations of serum gonadal hormones were detected with magnetic particle separation ELISA. RESULTS: During musk-secreting period, concentration changes of three serum gonadal hormones showed clear regularity, three crests occurred synchronously. Before musk-secreting period, testosterone, estradiol and progesterone concentrations were at its lower level, in prime musk-secreting period, they increased rapidly to respective highest peak; at later musk-secreting period, they quickly dropped to close to its previous levels before musk-secreting period. During estrus, serum testosterone concentration increased to lower peaks than that at later musk-secreting period. Estradiol remained at a low level and progesterone level was closed to zero. Serum testosterone concentrations in prime musk-secreting period were 114.4 ~ 190.5 times of estrus. During musk-secreting period, there were significant positive correlation among three serum gonadal hormone levels, a positive correlation between musk yield and serum testosterone levels, and negative correlation of musk yield with serum estradiol and progesterone levels as well as musk deer ages. CONCLUSION: Serum testosterone concentrations in prime musk-secreting period increase to the highest levels,which can provide reference in musk secretion induced by artificial means.

saRNA guided iNOS up-regulation improves erectile function of diabetic rats.

PURPOSE: Promoter targeted saRNAs mediate sequence specific up-regulation of gene expression. We explored the therapeutic effect of RNA activation mediated iNOS gene activation on improving erectile function in a rat model of diabetes mellitus. MATERIALS AND METHODS: An optimal saRNA sequence specific for iNOS promoter was cloned into an adenoviral vector, resulting in AdU6/shiNOS and AdU6/shControl. The corresponding viruses were used to transduce cultured rat cavernous smooth muscle cells. Streptozotocin induced diabetes models were established in rats and used to test the effects of intracavernous delivery of iNOS saRNA viruses on erectile function. iNOS expression in the cavernous smooth muscle cells or penile tissue of treated rats was assessed by reverse transcriptase-polymerase chain reaction and Western blot. Cyclic guanosine monophosphate was analyzed by enzyme-linked immunosorbent assay. Intracavernous pressure in response to cavernous nerve stimulation was measured using a data acquisition system on post-injection days 1, 3, 5, 7, 10 and 14. RESULTS: Adenovirus mediated expression of iNOS saRNA caused sustained up-regulation of iNOS in cavernous smooth muscle cells. Intracavernous injection of AdU6/shiNOS activated iNOS expression in vivo and significantly increased peak intracavernous pressure in streptozotocin induced diabetic rats via nitric oxide/intracellular cyclic guanosine monophosphate activation. CONCLUSIONS: Results show that saRNA mediated iNOS over expression in the penis can restore erectile function in streptozocin diabetic rats via the nitric oxide-cyclic guanosine monophosphate pathway.

[Preliminary analysis of chigger mite community on Eothenomys miletus in 19 counties of Yunnan province].

Eothenomys miletus were captured in 19 counties of Yunnan Province. The distribution of species-abundance and the species-plots relationship between E. miletus and chigger mites were analyzed by using ecological statistic method. There were totally 40,052 chigger mites collected from the body surface of 1741 E. miletus. 111 species of chigger mites were identified. The species-abundance distribution showed that with the increase of mite individuals, the number of chigger mite species gradually decreased. Most mite species were rare ones. Species-plot relation indicated that with the number of mouse plots (samples of E. miletus) increasing, the number of chigger mite species increased. E. miletus collected quantity up to date still could not reflect the exact species richness of chigger mite.

[Preliminary survey on the distribution of Leptotrombidium deliense in some areas of Yunnan province].

OBJECTIVE: To investigate the distribution of Leptotrombidium deliense among different small mammal hosts in some areas of Yunnan province. METHODS: A field survey was carried out in some counties of Yunnan province and the small mammal hosts were captured, using mouse cages and traps with baits. Chigger mites on the surface of two auricles were scraped off by a bistoury, and then preserved in 70% ethanol. Every specimen of the chigger mites on the slides was finally identified into species under a microscope. Some conventional statistical methods were adopted to calculate all the collected chigger mite species and the constituent ratios of Leptotrombidium deliense in different areas and on different hosts, together with its prevalence and mean abundance on different hosts. RESULTS: A total of 10 222 small mammal hosts were captured from 19 counties and identified as 11 families, 34 genera and 62 species in 5 orders, and 92 990 individuals of chigger mites were collected from the body surface of these small mammal hosts. All the collected chigger mites were identified as 3 subfamilies, 22 genera, and 225 species. Meanwhile, Leptotrombidium deliensee only accounted for 1.659% of the total. The host specificity of Leptotrombidium deliense was very low and 1544 individuals of Leptotrombidium deliense collected from 8518 small mammal hosts belonged to 6 families, 13 genera and 19 species in 3 orders. Our results showed that Leptotrombidium delienses were mainly collected from Insectivora and Rodentia. Leptotrombidium deliense had long been considered as the dominant species of chigger mites and the main vector of tsutsugamushi disease in Yunnan province of China, but our results seemed not thoroughly supporting this point of view. CONCLUSION: Traditionally, Leptotrombidium deliense was the dominant species and the main vectors of scrub typhus in Yunnan province. However, based on our results, the above view might be true in some local places and the composition of chigger mites and the main vector of tsutsugamushi disease might be different in regions and habitats in Yunnan province.

Host selection and niche differentiation in sucking lice (Insecta: Anoplura) among small mammals in southwestern China.

Understanding factors that shape host selection has been a classic issue in ecology, evolutionary biology, and epidemiological investigation. During the survey from 2000 to 2009, a total of 11,216 individuals of small mammals were captured from Yunnan Province in southwestern China. The captured small mammalian hosts belong to five orders, ten families, 35 genera, and 65 species and from their body surface, 38,885 individuals of ectoparasitic sucking lice were collected, which represent five families, seven genera, and 31 species. Based on niche overlap of dominant sucking lice on their primary hosts, we used hierarchical cluster analysis to sort different sucking louse species' resource utilizations of similar kind into respective categories. Given λ<5, there are only two groups clustered, however, sucking louse species' resource utilization was sorted into eight respective categories at λ=15. The results revealed that most species of sucking lice usually had high host specificity and a certain species of sucking louse usually restricted to one or few small mammalian species as their dominant hosts. Correspondence analysis was used to visualize associations between parasitic sucking lice and their small mammalian hosts, which suggested three different patterns of host resource utilization: species specialists, genera generalists, and multiple selections. For example, Sathrax durus (Johnson) only parasitized on species of Tupaia belangeri (Wagner), Hoplopleura edentula (Fahredholz) predominatly on genus of Eothenomys, and Polyplax reclinata (Nitzsch) on Family of Soricidae. Our results demonstrate that sucking lice have high host specificity and this might be due to coevolution between sucking lice and their hosts.

[Research on the area distribution and host selection of Leptotrombidium scutellare in 19 counties of Yunnan Province].

In order to investigate the area distribution and host selection of Leptotrombidium scutellare in Yunnan Province, a field survey was carried out during 2001 to 2009, based on different geographic location, topography, climate and ecological characteristics. A total of 16 491 L. scutellare were captured from the body surface of 9 838 small mammal hosts of 7 families, 18 genera, and 30 species in 4 orders, accounted for 17.73% (16,491/92,990) of all chigger mites collected. L. scutellare distributed in 12 counties, more in the northwest and south of the Province. Although L. scutellare could parasitize on different small mammal species, most of them were on Eothenomys miletus and Apodemus chevrieri.

[Application of PCR and related techniques in the examination of Orientia tsutsugamushi].

With the application of PCR technique in the medical field, PCR and its related techniques have made progress on detecting Orientia tsutsugamushi, which have played an important role in the early diagnosis of tsutsugamushi This paper summarizes the application of PCR and related techniques in detecting disease and pathogen research. This paper summarizes the application of PCR and related techniques in detecting O. tsutsugamushi.

The potential effect of proteasome inhibitor PS-341 on severe acute pancreatitis detected by positron emission tomography in ICR mice.

INTRODUCTION: Severe acute pancreatitis is a life threatening disease with a high rate of mortality, and its treatments are still controversial. The purpose of this study is to investigate the potential effects of proteasome inhibitor PS-341 on severe acute pancreatitis induced by cerulein and lipopolysaccharide in mice. MATERIALS AND METHODS: Severe acute pancreatitis was induced by seven intraperitoneal injections of 50 ug/kg cerulein at hourly intervals and one injection of 10mg/kg lipopolysaccharide in mice. Thirty min before the administration of lipopolysaccharide, mice were treated either with PS-341 or vehicle. The severity of acute pancreatitis was then evaluated by serum and pancreatic biochemical assays as well as histologic examination. Positron emission tomography (PET) was used for the first time to determine the therapeutic effects of interventions in situ. RESULTS: PS-341 significantly inhibited NF-kappaB activation, while the pancreatic cell apoptosis was significantly enhanced, resulting in the improved parameters such as serum amylase, C-reactive protein, lactate dehydrogenase, interleukin-1beta, interleukin-6, and pancreatic myeloperoxidase activity. Accordingly, pancreatic damage, including inflammatory cell infiltration, hemorrhage, and necrosis, was markedly reduced. (18)F-fluorodeoxyglucose-positron emission tomography demonstrated that PS-341 significantly reduced the uptake of (18)F-fluorodeoxyglucose within the pancreas. CONCLUSIONS: These observations demonstrate that PS-341 was able to significantly reduce the severity of acute pancreatitis induced by cerulein and lipopolysaccharide in mice. The potential effect is associated with the inhibition of NF-kappaB activation and increased pancreatic cell apoptosis within the pancreas. (18)F-fluorodeoxyglucose-positron emission tomography could be a sensitive and promising means in evaluating the therapeutic effect and adjusting medical interventions for pancreatitis.

[Growth process of Larix principis-rupprechtii stands with different density on south slope of Liupan Mountains].

By the method of sample trees stem analysis, this paper studied the growth process and diameter structure of 21-year-old Larix principis-rupprechtii plantations with the densities of 1200, 1500, and 2000 stems x hm(-2) in the head-water area on the southern slope of Liupan Mountain in Ningxia Hui Autonomous Region. The results showed that there were no significant differences in the growth status of L. principis-rupprechtii stands among the three densities when the stand age was less than 10 years. However, obvious differences were observed in the diameter and timber volume of individual trees and in the stand volume when the stand age was more than 10 years. The tree growth status in low-density stand was apparently better than that in medium- and high-density stands, but the height growth had no significant difference among the three densities. There was a significant difference in the skewness coefficient (Sk) of diameter distribution among the stands with different density, being higher (Sk = 0.338) in high-density stand than in medium-density stand (Sk = 0.072) and low-density stand (Sk = 0.015). The diameter distribution in high-density stand deviated from normal distribution, with a zenith tending to left, while that in medium- and low-density stands approached a normal distribution, with a more reasonable density structure. The kurtosis coefficient (K = 1.691) of medium-density stand was higher than that of high-density stand (K = 1.532) and low-density stand (K = 0.665), indicating a lower degree of polarization of tree growth in medium-density stand than in other two stands. The reasonable remaining density of 21-year-old L. principis-rupprechtii plantations was suggested to be 1200 stems x hm(-2).