RNAi of yellow-y, required for normal cuticle pigmentation, impairs courtship behavior and oviposition in the German cockroach (Blattella germanica).

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.

DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability.

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

The melanin pigment gene black mediates body pigmentation and courtship behaviour in the German cockroach Blattella germanica.

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.

Nanoparticle-delivered RNAi-based pesticide target screening for the rice pest white-backed planthopper and risk assessment for a natural predator.

Vacuolar-type (H+)-ATPase (vATPase) is a conserved multi-subunit eukaryotic enzyme composed of 14 subunits that form a functional complex consisting of an ATP-hydrolytic domain (V1) and a proton-translocation domain (V0). ATP hydrolysis and subsequent H+ translocation rely heavily on a fully assembled V1/V0 complex. Since vATPase is crucial for insect survival, it is a viable molecular target for pest control. However, detailed functional analyses of the 14 subunits and their suitability for pest control have not been fully explored in a single insect species. In this study, we identified 22 vATPase subunit transcripts that correspond to 13 subunits (A1, A2, B, C, D, E, F, G, H, a1, a2, c and d) in the white-backed planthopper (WBPH), Sogatella furcifera, a major hemipteran pest of rice. RNAi screens using microinjection and spray-based methods revealed that the SfVHA-F, SfVHA-a2 and SfVHA-c2 subunits are critical. Furthermore, star polymer (SPc) nanoparticles were utilized to conduct spray-induced and nanoparticle-delivered gene silencing (SI-NDGS) to evaluate the pest control efficacy of RNAi targeting the SfVHA-F, SfVHA-a2 and SfVHA-c2 transcripts. Target mRNA levels and vATPase enzymatic activity were both reduced. Honeydew excreta was likewise reduced in WBPH treated with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. To assess the environmental safety of the nanoparticle-wrapped dsRNAs, Cyrtorhinus lividipennis Reuter, a major natural enemy of planthoppers, was also sprayed with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. Post-spray effects of dsSfVHA-a2 and dsSfVHA-c2 on C. lividipennis were innocuous. This study identifies SfVHA-a2 and SfVHA-c2 as promising targets for biorational control of WBPH and lays the foundation for developing environment-friendly RNAi biopesticides.

RNA Interference-Screening of Potentially Lethal Gene Targets in the White-Backed Planthopper Sogatella furcifera via a Spray-Induced and Nanocarrier-Delivered Gene Silencing System.

RNA interference (RNAi) is a widespread post-transcriptional silencing mechanism that targets homologous mRNA sequences for specific degradation. An RNAi-based pest management strategy is target-specific and considered a sustainable biopesticide. However, the specific genes targeted and the efficiency of the delivery methods can vary widely across species. In this study, a spray-induced and nanocarrier-delivered gene silencing (SI-NDGS) system that incorporated gene-specific dsRNAs targeting conserved genes was used to evaluate phenotypic effects in white-backed planthopper (WBPH). At 2 days postspraying, transcript levels for all target genes were significantly reduced and knockdown of two gene orthologs, hsc70-3 and PP-α, resulted in an elevated mortality (>60%) and impaired ecdysis. These results highlight the utility of the SI-NDGS system for identifying genes involved in WBPH growth and development that could be potentially exploitable as high mortality target genes to develop an alternative method for WBPH control.

Efficient DIPA-CRISPR-mediated knockout of an eye pigment gene in the white-backed planthopper, Sogatella furcifera.

Although CRISPR/Cas9 has been widely used in insect gene editing, the need for the microinjection of preblastoderm embryos can preclude the technique being used in insect species with eggs that are small, have hard shells, and/or are difficult to collect and maintain outside of their normal environment. Such is the case with Sogatella furcifera, the white-backed planthopper (WBPH), a significant pest of Oryza sativa (rice) that oviposits inside rice stems. Egg extraction from the stem runs the risk of mechanical damage and hatching is heavily influenced by the micro-environment of the rice stem. To bypass these issues, we targeted embryos prior to oviposition via direct parental (DIPA)-CRISPR, in which Cas9 and single-guide RNAs (sgRNAs) for the WBPH eye pigment gene tryptophan 2,3-dioxygenase were injected into the hemocoel of adult females. Females at varying numbers of days posteclosion were evaluated to determine at what stage their oocyte might be most capable of taking up the gene-editing components. An evaluation of the offspring indicated that the highest G0 gene-edited efficacy (56.7%) occurred in females injected 2 d posteclosion, and that those mutations were heritably transmitted to the G1 generation. This study demonstrates the potential utility of DIPA-CRISPR for future gene-editing studies in non-model insect species and can facilitate the development of novel pest management applications.

Natural Products and Biological Activities of Plants from Genus Morus: 2011-2023.

Species of genus Morus (family Moraceae) have been used as traditional medicinal and edible resources since ancient times. Genus Morus has been acknowledged as a promising resource for the exploration of novel compounds with various bioactivities. Phytochemical investigations of the genus have led to the discovery of more than approximately 453 natural products from 2011 to 2023, mainly including flavonoids, Diels-Alder adducts, 2-arylbenzfuran, alkaloids and stilbenes. Bioactive constituents and extracts of this genus displayed a wide range of impressive biological properties including antidiabetic, anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, renoprotective, and some other activities. Herein, the research progress of this genus Morus from 2011 to 2023 on phytochemistry and pharmacology are systematically presented and discussed for the first time. This current review provides the easiest access to the information on genus Morus for readers and researchers in view of enhancing the continuity on research done on this genus.

The association between blood heavy metals and gallstones: A cross-sectional study.

BACKGROUND AND AIMS: Exposure to heavy metals has been widely recognized as a risk factor for human health. However, there is limited information on the effects of blood heavy metals on gallstones. This study aims to investigate the relationship between blood heavy metals and gallstones using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: 7192 participants aged 20 years or older with complete information were included in the study. Serum concentrations of heavy metals were determined by inductively coupled plasma kinetic reaction cell mass spectrometry. Gallstones were presented by standard questionnaires. Logistic regression, nonlinear, subgroup, and sensitivity analyses were used to estimate the association between blood heavy metals and gallstones. RESULTS: Multivariate logistic regression showed that the highest quintile of blood selenium (Se) was associated with a higher risk of gallstones compared with the lowest quintile (OR = 1.66, 95% CI: 1.16-2.36), particularly in individuals who were under 65 years of age, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. There was no correlation between blood cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and gallstones in the total population. Restricted cubic spline curves showed that a negative correlation was observed between blood Cd (OR = 0.84, 95% CI: 0.710-1.00), Hg (OR = 0.87, 95% CI: 0.78-0.97) and gallstones when Cd < 0.302 µg/L and Hg < 3.160 µg/L. CONCLUSIONS: Blood Se was an independent risk factor for gallstones, particularly in individuals under 65 years old, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. Furthermore, blood Cd and Hg were associated with a reduced risk of gallstones within a certain range.

DHCR24 reverses Alzheimer's disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice.

Accumulating evidences reveal that cellular cholesterol deficiency could trigger the onset of Alzheimer's disease (AD). As a key regulator, 24-dehydrocholesterol reductase (DHCR24) controls cellular cholesterol homeostasis, which was found to be downregulated in AD vulnerable regions and involved in AD-related pathological activities. However, DHCR24 as a potential therapeutic target for AD remains to be identified. In present study, we demonstrated the role of DHCR24 in AD by employing delivery of adeno-associated virus carrying DHCR24 gene into the hippocampus of 5xFAD mice. Here, we found that 5xFAD mice had lower levels of cholesterol and DHCR24 expression, and the cholesterol loss was alleviated by DHCR24 overexpression. Surprisingly, the cognitive impairment of 5xFAD mice was significantly reversed after DHCR24-based gene therapy. Moreover, we revealed that DHCR24 knock-in successfully prevented or reversed AD-related pathology in 5xFAD mice, including amyloid-ß deposition, synaptic injuries, autophagy, reactive astrocytosis, microglial phagocytosis and apoptosis. In conclusion, our results firstly demonstrated that the potential value of DHCR24-mediated regulation of cellular cholesterol level as a promising treatment for AD.

The antihyperuricemia activity of Astragali Radix through regulating the expression of uric acid transporters via PI3K/Akt signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is the dry root of the leguminous plants Astragalus membranaceus (Fisch) Beg. var. mongholicus (Beg) Hsiao, and Astragalus membranaceus (Fisch) Bge., being used as a medicinal and edible resource. AR is used in traditional Chinese medicine prescriptions to treat hyperuricemia, but this particular effect is rarely reported, and the associated mechanism of action is still need to be elucidated. AIM OF THE STUDY: To research the uric acid (UA)-lowering activity and mechanism of AR and the representative compounds through the constructed hyperuricemia mouse and cellular models. MATERIALS AND METHODS: In our study, the chemical profile of AR was analysed by UHPLC-QE-MS, as well as the mechanism of action of AR and the representative compounds on hyperuricemia was studied through the constructed hyperuricemia mouse and cellular models. RESULTS: The main compounds in AR were terpenoids, flavonoids and alkaloids. Mice group treated with the highest AR dosage showed significantly lower (p < 0.0001) serum uric acid (208 ± 9 µmol/L) than the control group (317 ± 11 µmol/L). Furthermore, UA increased in a dose-dependence manner in urine and faeces. Serum creatinine and blood urea nitrogen standards, as well as xanthine oxidase in mice liver, decreased (p < 0.05) in all cases, indicating that AR could relieve acute hyperuricemia. UA reabsorption protein (URAT1 and GLUT9) was down-regulated in AR administration groups, while the secretory protein (ABCG2) was up-regulated, indicating that AR could promote the excretion of UA by regulating UA transporters via PI3K/Akt signalling pathway. CONCLUSION: This study validated the activity, and revealed the mechanism of AR in reducing UA, which provided experimental and clinical basis for the treatment of hyperuricemia with it.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

Efficient nanoparticle-based CRISPR-Cas13d induced mRNA disruption of an eye pigmentation gene in the white-backed planthopper, Sogatella furcifera.

The discovery of the clustered regularly interspaced short palindromic repeat (CRISPR) system has driven gene manipulation technology to a new era with applications reported in organisms that span the tree of life. The utility of CRISPR-mediated editing was further expanded to mRNA following identification of the RNA-targeting Cas13 family of smaller endonuclease proteins. Application of this family to insect research, however, has been more limited. In this study, the smallest Cas13 family member, Cas13d, and guide RNAs (gRNAs) were complexed with a versatile nanomaterial (star polycation, SPc) to generate a proof-of-concept RNA-editing platform capable of disrupting mRNA expression of the eye pigmentation gene tryptophan 2,3-dioxygenase (SfTO) in white-backed planthoppers (WBPHs). The resulting red-eye phenotype was present in 19.76% (with SPc) and 22.99% (without SPc) of the treatment groups and was comparable to the red-eye phenotype generated following conventional RNA interference knockdown (22.22%). Furthermore, the Cas13/gRNA phenotype manifested more quickly than RNA interference. Consistent with the expected Cas13d mechanism, SfTO transcript levels were significantly reduced. Taken together, the results indicate that the SPc-CRISPR-Cas13d/gRNA complex negatively impacted expression of the target gene. These findings confirm the utility of this novel mRNA disruption system in insects and lay the foundation for further development of these tools in the implementation of green agricultural pest management tactics.

Functional characterization of five developmental signaling network genes in the white-backed planthopper: Potential application for pest management.

BACKGROUND: The white-backed planthopper (WBPH, Sogatella furcifera) is a major rice pest that exhibits condition dependent wing dimorphisms - a macropterous (long wing) form and a brachypterous (short wing) form. Although, the gene cascade that regulates wing development and dimorphic differentiation has been largely defined, the utility of these genes as targets for pest control has yet to be fully explored. RESULTS: Five genes typically associated with the developmental signaling network, armadillo (arm), apterous A (apA), scalloped (sd), dachs (d), and yorkie (yki) were identified from the WBPH genome and their roles in wing development assessed following RNA interference (RNAi)-mediated knockdown. At 5 days-post injection, transcript levels for all five targets were substantially decreased compared with the dsGFP control group. Among the treatment groups, those injected with dsSfarm had the most pronounced effects on transcript reduction, mortality (95 ± 3%), and incidence (45 ± 3%) of wing deformities, whereas those injected with dsSfyki had the lowest incidence (6.7 ± 4%). To assess the utility of topical RNAi for Sfarm, we used a spray-based approach that complexed a large-scale, bacteria-based double-stranded RNA (dsRNA) expression pipeline with star polycation (SPc) nanoparticles. Rice seedlings infested with third and fourth instar nymphs were sprayed with SPc-dsRNA formulations and RNAi phenotypic effects were assessed over time. At 2 days post-spray, Sfarm transcript levels decreased by 86 ± 9.5% compared with dsGFP groups, and the subsequent incidences of mortality and wing defects were elevated in the treatment group. CONCLUSIONS: This study characterized five genes in the WBPH developmental signaling cascade, assessed their impact on survival and wing development via RNAi, and developed a nanoparticle-dsRNA spray approach for potential field control of WBPH. © 2023 Society of Chemical Industry.

Two Antenna-Enriched Carboxylesterases Mediate Olfactory Responses and Degradation of Ester Volatiles in the German Cockroach Blattella germanica.

Insects have evolved an extremely sensitive olfactory system that is essential for a series of physiological and behavioral activities. Some carboxylesterases (CCEs) comprise a major subfamily of odorant-degrading enzymes (ODEs) playing a crucial role in odorant signal inactivation to maintain the odorant receptor sensitivity. In this study, 93 CCEs were annotated in the genome of the German cockroach Blattella germanica, a serious urban pest. Phylogenetic and digital tissue expression pattern analyses identified two antenna-enriched CCEs, BgerCCE021e3 and BgerCCE021d1, as candidate ODEs. RNA interference (RNAi)-mediated knockdown of BgerCCE021e3 and BgerCCE021d1 resulted in partial anosmia with experimental insects exhibiting reduced attraction to ester volatile resources and slower olfactory responses than controls. Furthermore, enzymatic conversion of geranyl acetate by crude male antennal extracts from BgerCCE021e3 and BgerCCE021d1 RNAi insects was also significantly reduced. Our results provide evidence for CCE function in German cockroach olfaction and provide a basis for further exploring behavioral inhibitors that target olfactory-related CCEs.

[Effect of Objective Daytime Sleepiness on Heart Rate Variability in Patients With Obstructive Sleep Apnea].

Objective: Excessive daytime sleepiness (EDS) is associated with cardiovascular events in patients with obstructive sleep apnea (OSA). Our study explored the correlation between objective daytime sleepiness assessed with daytime multiple sleep latency tests (MSLT) and heart rate variability (HRV) in OSA patients. The results may provide insight into possible mechanisms underlying increased risk of cardiovascular events in patients with OSA. Methods: A retrospective analysis was conducted with the data of 139 patients with OSA and 35 patients with primary snoring. All subjects underwent polysomnography (PSG) and MSLT at West China Hospital between January 2019 and May 2022. We used mean sleep latency (MSL) to measure the severity of EDS and to categorize OSA patients into three groups, severe EDS, light EDS, and non-EDS, with MSL of less than 5 minutes, 5 to 10 minutes, and greater than 10 minutes as the respective defining criteria for classification. A comparison of sleep structure, clinical characteristics, and HRV parameters was performed in order to evaluate the difference between OSA subgroups with varying levels of objective EDS and the primary snoring group. In addition, we also analyzed the correlation between MSL and HRV parameters. Results: Severe EDS patients had higher values of standard deviation of all N-N intervals (SDNN), total spectral power (TOT), and low-frequency power (LF) as compared to non-EDS patients, which was indicative of sympathetic stimulation ( P<0.05). Additionally, high-frequency power (HF) was also higher in severe EDS patients, which indicated decreased parasympathetic drive. A significantly positive correlation was found between MSL and the values of SDNN, TOT, LF, and HF in OSA patients. Conclusion: OSA patients with objective EDS have elevated sympathetic drive and decreased parasympathetic drive. A positive correlation was found between this change in neural activity and the shortening of MSL.

Functional characterization of tyrosine melanin genes in the white-backed planthopper and utilization of a spray-based nanoparticle-wrapped dsRNA technique for pest control.

As a significant pest of rice the white-backed planthopper (WBPH) Sogatella furcifera is a focus of pest management. However, traditional chemical-based control methods risk the development of pesticide resistance as well as severe ecological repercussions. Although nanoparticle-encapsulated dsRNAs provide a promising alternative method for sustainable pest management, gene targets specific to WBPH have yet to be optimized. Genes in the tyrosine-melanin pathway impact epidermal melanization and sclerotization, two processes essential for insect development and metabolism, have been proposed as good candidate targets for pest management. Seven genes (aaNAT, black, DDC, ebony, tan, TH, and yellow-y) in this group were identified from WBPH genome and functionally characterized by using RNAi for their impact on WBPH body color, development, and mortality. Knockdown of SfDDC, Sfblack, SfaaNAT, and Sftan caused cuticles to turn black, whereas Sfyellow-y and Sfebony knockdown resulted in yellow coloration. SfTH knockdown resulted in pale-colored bodies and high mortality. Additionally, an Escherichia coli expression system for large-scale dsRNA production was coupled with star polycation nanoparticles to develop a sprayable RNAi method targeting SfTH that induced high WBPH mortality rates on rice seedlings. These findings lay the groundwork for the development of large-scale dsRNA nanoparticle sprays as a WBPH control method.

Will male semen quality improve with environmental quality?

Wenzhou has improved its environmental quality because of comprehensive environmental remediation; nevertheless, the semen quality of infertile males remains unclear. This study determined whether better environmental quality improved semen quality in this region. We recorded semen quality data from 22 962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). Patients were predominantly 30-35 years old (33.1%) and workers (82.0%), with high school education or lower (77.6%); more than a half of the patients (52.6%) were Wenzhou household registration; and most patients (77.5%) had abnormal semen quality. Patients who were older than 40 years and workers, and those with Wenzhou household registration, had significantly worse semen quality (all P < 0.05). From 2014 to 2019, progressive sperm motility, total sperm motility, and semen volume showed increasing linear trends in all patients (P = 0.021, 0.030, and 0.005, respectively), yet normal sperm morphology showed a linearly decreasing trend (P = 0.046). Sensitivity analyses for subgroups yielded similar results. In conclusion, the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility, total sperm motility, and semen volume. Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.

Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-ß1/SMAD3 and JNK axis activation.

Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). It is also correlated to transforming growth factor-ß1 (TGF-ß1) expression, a crucial mediator in the interaction of cancer cells with TME. In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-ß expression (r = 0.7125). The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-ß1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression.

Functional characterization of developmentally critical genes in the white-backed planthopper: Efficacy of nanoparticle-based dsRNA sprays for pest control.

BACKGROUND: Epidermal growth factor receptor (EGFR), zinc finger homeodomain-2 (zfh-2), Abdominal-A (Abd-A), and Abdominal-B (Abd-B) regulate the growth and development of the insect abdomen. However, their potential roles in pest control have not been fully assessed. The development of insecticide resistance to multiple chemistries in the white-backed planthopper (WBPH), a major pest of rice, has prompted interest in novel pest control approaches that are ecologically friendly. Although pest management approaches based on double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) have potential, their susceptibility to degradation limits large-scale field applications. These limitations, however, can be overcome with nanoparticle-dsRNA complexes that have greater environmental stability and improved cellular uptake. RESULTS: In this study, at 5 days post-injection, transcripts for the four gene targets were reduced relative to controls and all of the experimental groups exhibited significant phenotypic defects and increased mortality. To evaluate the potential of these gene targets for field applications, a nanocarrier-dsRNA spray delivery system was assessed for RNAi efficacy. At 11 days post-spray, significant phenotypic defects and increased mortality were observed in all experimental groups. CONCLUSION: Taken together, the results confirm the suitability of the target genes (SfEGFR, Sfzfh-2, SfAbd-A, and SfAbd-B) for pest management and demonstrate the efficacy of the nanocarrier spray system for inducing RNAi-mediated knockdown. As such, the study lays the foundation for the further development and optimization of this technology for large-scale field applications. © 2022 Society of Chemical Industry.