Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated mRNA, microRNA transcriptome and degradome analyses provide insights into stamen development in moso bamboo.

The flower is essential for sexual reproduction of flowering plants and has been extensively studied in model plants. Here, we used transcriptomic, small RNA and degradome analyses to characterize key miRNAs and their targets in floral organs of moso bamboo. In total, we identified 13,051 differentially expressed genes (DEGs) and 109 known miRNAs from 26 miRNA families. We aligned the miRNAs to known miRNA databases and revealed some conserved as well as novel miRNAs. Sixteen conserved miRNAs were specific highly expressed in stamens, including miRNA159 and miRNA166. In situ hybridization shows that miRNA159 plays an key role in the regulation of stamen development and expression levels of its targets PheMYB98 and PheMYB42 were low. Furthermore, Phe-MIRNA159, partially recover phenotypes of mir159ab double mutant. Overexpression of Phe-MIR159 could cause anther dehisce failure, the mature pollens could not be dispersed and further reduce fertility in Arabidopsis. Semi-thin section result shows that anther endothelial layer of Phe-MIRNA159 overexpressing lines is lack of secondary thickening, resulting in limited force for anther opening. Phe-miR159 may regulate expression of genes related to secondary thickening through negative regulation of AtMYB33, affecting the anther dehiscence. Together, this study provides insights regarding molecular networks underlying floral organs development of moso bamboo.
Electrophysiological and Molecular Characterization of the Parasubiculum

The parahippocampal region is thought to be critical for memory and spatial navigation. Within this region lies the parasubiculum, a small structure that exhibits strong theta modulation, contains functionally specialized cells, and projects to layer II of the medial entorhinal cortex (MEC). Thus, it is uniquely positioned to influence firing of spatially modulated cells in the MEC and play a key role in the internal representation of the external environment. However, the basic neuronal composition of the parasubiculum remains largely unknown, and its border with the MEC is often ambiguous. We combine electrophysiology and immunohistochemistry in adult mice (both sexes) to define first, the boundaries of the parasubiculum, and second, the major cell types found in this region. We find distinct differences in the colabeling of molecular markers between the parasubiculum and the MEC, allowing us to clearly separate the two structures. Moreover, we find distinct distribution patterns of different molecular markers within the parasubiculum, across both superficial-deep and DV axes. Using unsupervised cluster analysis, we find that neurons in the parasubiculum can be broadly separated into three clusters based on their electrophysiological properties, and that each cluster corresponds to a different molecular marker. We demonstrate that, while the parasubiculum aligns structurally to some to general cortical principals, it also shows divergent features in particular in contrast to the MEC. This work will form an important basis for future studies working to disentangle the circuitry underlying memory and spatial navigation functions of the parasubiculum. SIGNIFICANCE STATEMENT We identify the major neuron types in the parasubiculum using immunohistochemistry and electrophysiology, and determine their distribution throughout the parasubiculum. We find that the neuronal composition of the parasubiculum differs considerably compared with the neighboring medial entorhinal cortex. Both regions are involved in spatial navigation. Thus, our findings are of importance for unraveling the underlying circuitry of this process and for determining the role of the parasubiculum within this network.
Fibromyalgia and Shoulder Surgery: A Systematic Review and a Critical Appraisal of the Literature

Fibromyalgia is a common musculoskeletal syndrome characterized by chronic widespread pain and other systemic manifestations, which has demonstrated a contribution to higher postoperative analgesic consumption to other surgeries such as hysterectomies and knee and hip replacements. The aim of this review is to search current literature for studies considering the impact of fibromyalgia on clinical outcomes of patients undergoing shoulder surgery. A systematic literature review was conducted in PubMed/Medline, Embase, and ClinicalTrials.gov in February 2019. Studies were selected based on the following participants, interventions, comparisons, outcomes, and study design criteria: adult patients undergoing surgery for shoulder pain (P); diagnosis of fibromyalgia (I); patients without fibromyalgia (C); outcome of surgery in terms of pain or analgesic or non-steroidal anti-inflammatory drugs consumption (O); case series, retrospective studies, observational studies, open-label studies, randomized clinical trials, systematic reviews and meta-analyses were included (S). Authors found 678 articles, of which four were found eligible. One retrospective study showed that patients with fibromyalgia had worse clinical postoperative outcomes; two retrospective studies reported a higher opioid prescription in patients with fibromyalgia and one prospective observational study found that a higher fibromyalgia survey score correlated with lower quality of recovery scores two days after surgery. The scarce and low-quality evidence available does not allow confirming that fibromyalgia has an impact on postoperative outcomes in shoulder surgery. Future studies specifically focusing on shoulder surgery outcomes may help improvement and personalization of the management of patients with fibromyalgia syndrome (PROSPERO 2019, CRD42019121180).
Microfluidic-Based Mechanical Phenotyping of Androgen-Sensitive and Non-sensitive Prostate Cancer Cells Lines

Cell mechanical properties have been identified to characterize cells pathologic states. Here, we report our work on high-throughput mechanical phenotyping of androgen-sensitive and non-sensitive human prostate cancer cell lines based on a morphological rheological microfluidic method. The theory for extracting cells’ elastic modulus from their deformation and area, and the used experimental parameters were analyzed. The mechanical properties of three types of prostate cancer cells lines with different sensitivity to androgen including LNCaP, DU145, and PC3 were quantified. The result shows that LNCaP cell was the softest, DU145 was the second softest, and PC3 was the stiffest. Furthermore, atomic force microscopy (AFM) was used to verify the effectiveness of this high-throughput morphological rheological method.
The Impact of Cold and Heat on Years of Life Lost in a Northwestern Chinese City with Temperate Continental Climate

Cold spells and heat waves in a changing climate are well known as great public-health concerns due to their adverse effects on human health. However, very few studies have quantified health impacts of heat and cold in the region of Northwestern China. The purpose of the present study was to evaluate the effects of cold and heat on years of life lost (YLL) in Lanzhou, a city with temperate continental climate. We compiled a daily dataset including deaths, weather variables, and air pollutants in Lanzhou, China, from 2014-2017. We used a distributed lag non-linear model to estimate single-day and cumulative effects of heat and cold on daily YLL. Results indicated that both cold and heat were associated with increased YLL for registered residents in Lanzhou. Estimated heat effects appeared immediately in the first two days, while estimated cold effects lasted over a longer period (up to 30 days). Cold significantly increased the YLL of all residents except for males and those with respiratory diseases (≥65 years). Our results showed that both heat and cold had more pronounced effects on cardiovascular diseases compared to respiratory diseases. Males might be more vulnerable to heat, while females might suffer more YLL from cold. The effects of cold or heat on the elderly might appear earlier and last longer than those for other age groups.
An autism-associated mutation in GluN2B prevents NMDA receptor trafficking and interferes with dendrite growth

ABSTRACT Autism spectrum disorders (ASDs) are neurodevelopmental disorders with multiple genetic associations. Analysis of de novo mutations identified GRIN2B, which encodes the GluN2B subunit of NMDA receptors, as a gene linked to ASDs with high probability. However, the mechanisms by which GRIN2B mutations contribute to ASD pathophysiology are not understood. Here, we investigated the cellular phenotypes induced by a human mutation that is predicted to truncate GluN2B within the extracellular loop. This mutation abolished NMDA-dependent Ca2+ influx. Mutant GluN2B co-assembled with GluN1 but was not trafficked to the cell surface or dendrites. When mutant GluN2B was expressed in developing cortical neurons, dendrites appeared underdeveloped, with shorter and fewer branches, while spine density was unaffected. Mutant dendritic arbors were often dysmorphic, displaying abnormal filopodial-like structures. Interestingly, dendrite maldevelopment appeared when mutant GluN2B was expressed on a wild-type background, reflecting the disease given that individuals are heterozygous for GRIN2B mutations. Restoring the fourth transmembrane domain and cytoplasmic tail did not rescue the phenotypes. Finally, abnormal development was not accompanied by reduced mTOR signaling. These data suggest that mutations in GluN2B contribute to ASD pathogenesis by disrupting dendrite development. Highlighted Article: GRIN2B mutations cause ASD, but the pathogenic mechanisms remained unknown. We show that ASD-specific GRIN2B mutations interfere with NMDA receptor trafficking and lead to reduced dendrite elongation and branching.
Genome-Wide Analysis of Cotton Auxin Early Response Gene Families and Their Roles in Somatic Embryogenesis

Auxin is well known to regulate growth and development processes. Auxin early response genes serve as a critical component of auxin signaling and mediate auxin regulation of diverse physiological processes. In the present study, a genome-wide identification and comprehensive analysis of auxin early response genes were conducted in upland cotton. A total of 71 auxin response factor (ARF), 86 Auxin/Indole-3-Acetic Acid (Aux/IAA), 63 Gretchen Hagen3 (GH3), and 194 small auxin upregulated RNA (SAUR) genes were identified in upland cotton, respectively. Phylogenetic analysis revealed that the ARF, GH3, and SAUR families were likely subject to extensive evolutionary divergence between Arabidopsis and upland cotton, while the Aux/IAA family was evolutionary conserved. Expression profiles showed that the ARF, Aux/IAA, GH3, and SAUR family genes were extensively involved in embryogenic competence acquisition of upland cotton callus. The Aux/IAA family genes generally showed a higher expression level in the non-embryogenic callus (NEC) of highly embryogenic cultivar CCRI24 than that of recalcitrant cultivar CCRI12, which may be conducive to initializing the embryogenic transformation. Auxin early response genes were tightly co-expressed with most of the known somatic embryogenesis (SE) related genes, indicating that these genes may regulate upland cotton SE by interacting with auxin early response genes.
Surface Exposure of PEG and Amines on Biodegradable Nanoparticles as a Strategy to Tune Their Interaction with Protein-Rich Biological Media

Nanoparticles (NPs) based on amphiphilic block copolymers of polyethylene glycol (PEG) and biodegradable polyesters are of particular current interest in drug nanodelivery due to their easily manipulated properties. The interaction of these NPs with biological environments is highly influenced by shell features, which drive biological identity after administration. To widen the strategies available for tuning particle surface chemistry, here we developed a panel of amine-bearing PEGylated NPs with a poly(ε-caprolactone) (PCL) core for the delivery of lipophilic drugs, and investigated the impact of NP modifications on their interaction with abundant circulating proteins (human serum albumin—HSA—and mucin), as well as their transport through biological barriers (artificial mucus—AM, extracellular matrix—ECM). We prepared NPs based on a diamino-terminated PCL (amine-NPs) and its mixture with PEG-PCL copolymers (amine/PEG-NPs) at different PEG molecular weights by nanoprecipitation, as well as corresponding NPs of PEG-PCL (PEG-NPs). The presence of an amine-bearing polymer resulted in NPs with a net positive charge and a zeta potential dependent on the length of PEG in the copolymer. Amine/PEG-NPs had a larger fixed aqueous layer thickness as compared to PEG-NPs, suggesting that PEG conformation is affected by the presence of positive charges. In general, amine-bearing NPs promptly interacted with the dysopsonic protein HSA, due to electrostatic interactions, and lose stability, thereby undergoing time-related aggregation. On the other hand, amine/PEG-NPs interaction with mucin induced switching to a negative surface charge but did not alter the quality of the dispersion. The transport kinetics of NPs through a layer of artificial mucus and tumor extracellular matrix was studied by means of fluorescent NPs based upon FRET. Amine/PEG-NPs did not cross the ECM, but they were promptly transported through the AM, with swifter transport noted at increasing MWs of PEG in the copolymer. Finally, we demonstrated that all the different NP types developed in this study are internalized by human monocytes and, despite the positive charge, they did not induce a measurable inflammatory effect. In conclusion, we showed that the concurrent presence of both PEG and amine groups on NP surface is a promising strategy for directing their interaction with body compartments. While PEG-NPs are confirmed for their capacity to cross ECM-like compartments, amine/PEG-NPs are revealed as a powerful platform to widen the arsenal of nanotools available for overcoming mucus-covered epithelia.
Obligate intracellular bacteria diversity in unfed Leptotrombidium scutellare larvae highlights novel bacterial endosymbionts of mites

It is well known that the mite Leptotrombidium scutellare carries the pathogen of scrub typhus, Orientia tsutsugamushi. However, our understanding of other bacterial endosymbionts of mites is limited. This study investigated the diversity of the obligate intracellular bacteria carried by L. scutellare using 16S rRNA gene amplicon analysis with next‐generation sequencing. The results showed that the detected bacteria were classified into the genera Rickettsia, Wolbachia, and Rickettsiella and an unknown genus of the order Rickettsiales. For further classification of the detected bacteria, a representative read that was most closely related to the assigned taxonomic classification was subjected to homology search and phylogenic analysis. The results showed that some bacteria of the genus Rickettsia were identical or very close to the human pathogens Rickettsia akari, Rickettsia aeschlimannii, Rickettsia felis, and Rickettsia australis. The genetic distance between the genus Wolbachia bacteria in the present study and in previous reports is highly indicative that the bacteria in the present study can be classified as a new taxon of Wolbachia. This study detected obligate intracellular bacteria from unfed mites; thus, the mites did not acquire bacteria from infected animals or any other infectious sources. Finally, the present study demonstrated that various and novel bacterial endosymbionts of mites, in addition to O. tsutsugamushi, might uniquely evolve with the host mites throughout overlapping generations of the mite life cycle. The roles of the bacteria in mites and their pathogenicity should be further examined in studies based on bacterial isolation.
Human-mimetic soft robot joint for shock absorption through joint dislocation

This paper presents a human-mimetic manipulator capable of shock absorption by using dislocation at the soft joint. A one degree-of-freedom (DOF) soft robot joint was developed based on the human elbow-joint structure, especially mimicking the humeroulnar joint in the elbow. Each component of the soft joint is combined by an elastic ligament, which is made up of elastic rubber and is attached to the pivot joint pin positioned at a predetermined place according to a specially designed pin guide. As an external impact is applied to the joint, the elastic ligament is elongated as the pivot joint pin is moved from the predetermined place. This state is defined as a dislocation, which is similar to the dislocation of a human joint when impacted. Dislocation in the proposed soft robot joint occurred when the external impact was larger than the predetermined threshold force. This threshold force can be predicted by the modulus of the elastic ligament and the shape of the pin guide, and the theoretical model was developed in this study. To evaluate the function of dislocation, dynamic and quasi-static impact tests were performed at the 1-DOF soft robot joint. Moreover, the human-mimetic manipulator is proposed based on the 2-DOF soft robot joint. This manipulator can realize four motions of a human arm using the pneumatic artificial muscles: flexion, extension, pronation and supination. Each artificial muscle and bone structure were similar to the human arm structure, and thus the configuration of each bone structure of the manipulator for each motion is similar to the configurations of a human skeletal structure. This manipulator was also capable of dislocation to absorb the external impact. The developed human-mimetic manipulator with a soft joint is expected to be applied to a naturally safe humanoid robot that works with humans in the same space.
Nicotinic Acetylcholine Receptor Subunit Alpha-5 Promotes Radioresistance via Recruiting E2F Activity in Oral Squamous Cell Carcinoma

Radiotherapy is commonly used to treat patients with oral squamous cell carcinoma (OSCC), but a subpopulation of OSCC patients shows a poor response to irradiation treatment. Therefore, identifying a biomarker to predict the effectiveness of radiotherapy in OSCC patients is urgently needed. In silico analysis of public databases revealed that upregulation of CHRNA5, the gene encoding nicotinic acetylcholine receptor subunit alpha-5, is extensively detected in primary tumors compared to normal tissues and predicts poor prognosis in OSCC patients. Moreover, CHRNA5 transcript level was causally associated with the effective dose of irradiation in a panel of OSCC cell lines. Artificial silencing of CHRNA5 expression enhanced, but nicotine reduced, the radiosensitivity of OSCC cells. Gene set enrichment analysis demonstrated that the E2F signaling pathway is highly activated in OSCC tissues with high levels of CHRNA5 and in those derived from patients with cancer recurrence after radiotherapy. CHRNA5 knockdown predominantly suppressed E2F activity and decreased the phosphorylation of the Rb protein; however, nicotine treatment dramatically promoted E2F activity and increased Rb phosphorylation, which was mitigated after CHRNA5 knockdown in OSCC cells. Notably, the signature combining increased mRNA levels of CHRNA5 and the E2F signaling gene set was associated with worse recurrence-free survival probability in OSCC patients recorded to be receiving radiotherapy. Our findings suggest that CHRNA5 is not only a useful biomarker for predicting the effectiveness of radiotherapy but also a druggable target to enhance the cancericidal effect of irradiation on OSCC.
Gemination in Northern versus Central and Southern Varieties of Italian: A Corpus-based Investigation

It is often claimed that patterns of gemination are different across varieties of Italian. In particular, northern speakers are sometimes said to degeminate, or to produce shorter geminates than central and southern speakers. However, experimental data proving such claims is largely missing. In this article, we perform an analysis of the CLIPS corpus with the aim of comparing gemination for northern versus central and southern speakers of Italian. The analysis of different data types (target words in isolated position, read sentences, dialogues, local radio and TV broadcasts) revealed that: (a) geminate consonants are produced by all speakers, incl. northern speakers; (b) differences in the magnitude of consonant lengthening are small (< 19 ms) and reach significance only for some data types; (c) the shortening of vowels preceding geminate consonants is mainly restricted to isolated target words in nuclear position, with no significant differences between northern and central/southern speakers. We argue that regional differences in Italian gemination have been overestimated and overemphasized in the literature. In fact, the evidence suggests that they are not as sizeable as previously thought, probably because of the progressive standardization of the language.
Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation

In thrombolytic therapy, plasminogen activators (PAs) are still the only group of drug approved to induce thrombolysis, and therefore, critical for treatment of arterial thromboembolism, such as stroke, in the acute phase. Functionalized nanocomposites have attracted great attention in achieving target thrombolysis due to favorable characteristics associated with the size, surface properties and targeting effects. Many PA-conjugated nanocomposites have been prepared and characterized, and some of them has been demonstrated with therapeutic efficacy in animal models. To facilitate future translation, this paper reviews recent progress of this area, especially focus on how to achieve reproducible thrombolysis efficacy in vivo.
Using an Overlapping Time Interval Strategy to Study Diagnostic Instability in Mild Cognitive Impairment Subtypes

(1) Background: Mild cognitive impairment (MCI) is a diagnostic label in which stability is typically low. The aim of this study was to examine temporal changes in the diagnosis of MCI subtypes by using an overlapping-time strategy; (2) Methods: The study included 435 participants aged over 50 years with subjective cognitive complaints and who completed at least one follow-up evaluation. The probability of transition was estimated using Bayesian odds ratios; (3) Results: Within the different time intervals, the controls with subjective cognitive complaints represented the largest proportion of participants, followed by sda-MCI at baseline and in the first five intervals of the follow-up, but not in the last eight intervals. The odds ratios indicated higher odds of conversion to dementia in sda-MCI and mda-MCI groups relative to na-MCI (e.g., interval 9–15 months—sda-MCI OR = 9 and mda-MCI OR = 3.36; interval 27–33—sda-MCI OR = 16 and mda-MCI = 5.06; interval 42–48—sda-MCI OR = 8.16 and mda-MCI = 3.45; interval 45–51—sda-MCI OR = 3.31 and mda-MCI = 1); (4) Conclusions: Notable patterns of instability consistent with the current literature were observed. The limitations of a prospective approach in the study of MCI transitions are discussed.