Soil microbial subcommunity assembly mechanisms are highly variable and intimately linked to their ecological and functional traits.

Revealing the mechanisms underlying soil microbial community assembly is a fundamental objective in molecular ecology. However, despite increasing body of research on overall microbial community assembly mechanisms, our understanding of subcommunity assembly mechanisms for different prokaryotic and fungal taxa remains limited. Here, soils were collected from more than 100 sites across southwestern China. Based on amplicon high-throughput sequencing and iCAMP analysis, we determined the subcommunity assembly mechanisms for various microbial taxa. The results showed that dispersal limitation and homogenous selection were the primary drivers of soil microbial community assembly in this region. However, the subcommunity assembly mechanisms of different soil microbial taxa were highly variable. For instance, the contribution of homogenous selection to Crenarchaeota subcommunity assembly was 70%, but it was only around 10% for the subcommunity assembly of Actinomycetes, Gemmatimonadetes and Planctomycetes. The assembly of subcommunities including microbial taxa with higher occurrence frequencies, average relative abundance and network degrees, as well as wider niches tended to be more influenced by homogenizing dispersal and drift, but less affected by heterogeneous selection and dispersal limitation. The subcommunity assembly mechanisms also varied substantially among different functional guilds. Notably, the subcommunity assembly of diazotrophs, nitrifiers, saprotrophs and some pathogens were predominantly controlled by homogenous selection, while that of denitrifiers and fungal pathogens were mainly affected by stochastic processes such as drift. These findings provide novel insights into understanding soil microbial diversity maintenance mechanisms, and the analysis pipeline holds significant value for future research.

Channel power management of 400†G transmission system based on C6T + L6†T spectrum and QPSK modulation format.

In the 400 Gbit/s transmission system based on C + L band spectrum and QPSK modulation format, the short-wavelength signal power will be shifted to the long-wavelength signal due to the presence of the stimulated Raman scattering (SRS) effect, which will seriously affect the performance of the transmission system as the transmission span accumulates. The solution is to set the gain and gain slopes of the C-band amplifier and L-band amplifier appropriately at each optical amplifier site, and adjust the signal power of each channel through the WSS at the transmitting end and the WSS at the DGE site, so that the flatness of the channel power at the receiving end can be controlled in a reasonable range, thus guaranteeing the transmission performance of the system. However, the system fault will destroy the originally set channel power, which will seriously affect the transmission performance of the system. In this paper, filling channel device combined with output power locking of amplifiers used in a 400 Gbit/s system based on C + L band and QPSK modulation format to provide the protection for the system is proposed and demonstrated for the first time, which gives different solutions for sudden fault at different locations of the system, and provides a reference for the channel power management of multi-band optical transmission systems in the future.

Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study.

BACKGROUND: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments. METHODS: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1-18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended. FINDINGS: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6-10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37-41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89-100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4-20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66-91), duration of remission was 80% (68-92), and disease-free survival was 80% (68-92) with transplantation censoring; overall survival was 96% (91-100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7-14) after CD19-directed and 12 days (10-15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia. INTERPRETATION: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition. FUNDING: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Facile and Universal Defect Engineering Toward Highly Stable Carbon-Based Polymer Brushes with High Grafting Density.

Carbon-based polymer brushes (CBPBs) are an important class of functional polymer materials, which synergistically combine the advantageous properties of both carbons and polymers. However, the conventional fabrication procedures of CBPBs involve tedious multistep modification, including preoxidation of carbon substrates, introduction of initiating groups, and subsequent graft polymerization. In this study, a simple yet versatile defect-engineering strategy is proposed for the efficient synthesis of high-grafting-density CBPBs with highly stable CC linkages via free radical polymerization. This strategy involves the introduction and removal of nitrogen heteroatoms in the carbon skeletons via a simple temperature-Fmed heat treatment, leading to the formation of numerous carbon defects (e.g., pentagons, heptagons, and octagons) with reactive C=C bonds in the carbon substrates. The as-proposed methodology enables the facile fabrication of CBPBs with various carbon substrates and polymers. More importantly, the highly grafted polymer chains in the resulting CBPBs are tethered with the carbon skeletons by robust CC bonds, which can endure strong acid and alkali environments. These interesting findings will shed new light on the well-orchestrated design of CBPBs and broaden their applications in various areas with fascinating performances.

Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse.

CONTEXT AND AIMS: Melatonin is a powerful antioxidant regulating various biological functions, including alleviating male reproductive damage under pathological conditions. Here, we aim to analyse the effect of melatonin on normal male reproduction in mice. METHODS: Male mice received an intraperitoneal injection of melatonin (10mg/kg body weight) for 35 consecutive days. The testis and epididymis morphology, and epididymal sperm parameters were examined. PCNA, HSPA2, SYCP3, ZO-1 and CYP11A1 expressions in epididymis or testis were detected by immunohistochemistry or Western blotting. Male fertility was determined by in vivo and in vitro fertilisation (IVF) experiments. The differentially expressed sperm proteins were identified by proteomics. KEY RESULTS: No visible structural changes and oxidative damage in the testis and epididymis, and no significant side effects on testis weight, testosterone levels, sperm motility, and sperm morphology were observed in the melatonin-treatment group compared with the control group. Spermatogenesis-related molecules of PCNA, SYCP3, ZO-1, and CYP11A1 showed no significant differences in melatonin-treated testis. However, PCNA and HSPA2 increased their expressions in the epididymal initial segments in the melatonin-treatment group. Normal sperm fertilisation, two-cell and blastocyst development were observed in the melatonin-treated group, but melatonin significantly enhanced the sperm binding ability characterised as more sperm binding to one oocyte (control 7.2±1.3 versus melatonin 11.8±1.5). Sperm proteomics demonstrated that melatonin treatment enhanced the biological process of cell adhesion in sperm. CONCLUSIONS AND IMPLICATIONS: This study suggests that melatonin can promote sperm maturation and sperm function, providing important information for further research on the physiological function and protective effect of melatonin in male reproduction.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) alleviate paclitaxel-induced spermatogenesis defects and maintain male fertility.

Chemotherapeutic drugs can cause reproductive damage by affecting sperm quality and other aspects of male fertility. Stem cells are thought to alleviate the damage caused by chemotherapy drugs and to play roles in reproductive protection and treatment. This study aimed to explore the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on alleviating paclitaxel (PTX)-induced spermatogenesis and male fertility defects. An in vivo PTX-induced mice model was constructed to evaluate the reproductive toxicity and protective roles of hUC-MSCs in male fertility improvement. A 14 day PTX treatment regimen significantly attenuated mice spermatogenesis and sperm quality, including affecting spermatogenesis, reducing sperm counts, and decreasing sperm motility. hUC-MSCs treatment could significantly improve sperm functional indicators. Mating experiments with normal female mice and examination of embryo development at 7.5 days post-coitum (dpc) showed that hUC-MSCs restored male mouse fertility that was reduced by PTX. In IVF experiments, PTX impaired sperm fertility and blastocyst development, but hUC-MSCs treatment rescued these indicators. hUC-MSCs' protective role was also displayed through the increased expression of the fertility-related proteins HSPA2 and HSPA4L in testes with decreased expression in the PTX-treated group. These changes might be related to the PTX-induced decreases in expression of the germ cell proliferation protein PCNA and the meiosis proteins SYCP3, MLH1, and STRA8, which were restored after hUC-MSCs treatment. In the PTX-treated group, the expression of testicular antioxidant proteins SIRT1, NRF2, CAT, SOD1, and PRDX6 was significantly decreased, but hUC-MSCs could maintain these expressions and reverse PTX-related increases in BAX/BCL2 ratios. hUC-MSCs may be a promising agent with antioxidant and anti-apoptosis characteristics that can maintain sperm quality following chemotherapy treatment.

Melatonin ameliorates paclitaxel-induced mice spermatogenesis and fertility defects.

Chemotherapeutic drug of paclitaxel (PTX) has been shown to cause reproductive toxicity thus affecting male fertility, but its underlying molecular basis is unclear. Melatonin (MLT) can mitigate the reproductive damage caused by certain chemotherapy drugs. In this study, we aimed to identify impact of PTX on the main biological processes and protective effect of MLT on reproductive damage caused by PTX. Mice exposed to PTX mainly impaired spermatogenesis, such as decreased sperm counts, reduced sperm motility and increased abnormal sperm. Decreased expressions of germ cell proliferation-associated protein PCNA and meiosis-related protein SYCP3 induced by PTX were determined by Western blot, while MLT ameliorated this effect and increased the expressions of PCNA, SYCP3, DMC1, STRA8 and fertility-related protein of HSPA2, resulting in significantly improved spermatogenesis and sperm quality levels. In vitro fertilization experiment showed that PTX significantly decreased blastocyst formation rates, which can be improved by MLT administration, but not two-cell development rates. Taken together, this work demonstrated PTX can adversely affect germ cell proliferation and meiosis, which ultimately influence sperm quality and male fertility, and highlighted the protective ability of MLT on ameliorating the side effects of PTX, especially on sperm quality. The results provide information to further the study on the molecular mechanism of PTX's effects on male reproduction and the protective mechanism of MLT.

Compact Tri-FFPI sensor for measurement of ultrahigh temperature, vibration acceleration, and strain.

As a high-precision fiber optic sensor, a single optical fiber Fabry Pérot interferometer (FFPI) sensor is often used to measure parameters such as temperature or strain. However, the use of combined FFPIs to measure multiple parameters simultaneously has rarely been reported. In this paper, a compact Tri-FFPI sensor consisting of three series-connected FFPIs is proposed to measure high temperature, high acceleration, and large strain. The total length and diameter of the sensing part are only 2558.9 µm and 250 µm, respectively. One of the FFPIs, FFPI-1, contains a cantilever beam structure to measure vibration acceleration. FFPI-2 is used to measure temperature and the temperature compensation of the strain measurement. FFPI-3 is used to measure strain. To ensure that the sensor has high measurement sensitivity, two demodulation methods are used: the light intensity demodulation method for vibration acceleration and the wavelength demodulation method for temperature and strain. The sensor is capable of withstanding ultrahigh temperatures up to 1000°C.

High-security SCMA-OFDM multi-core fiber transmission system based on a regular hexagon chaotic codebook.

Sparse code multiple access (SCMA), a new code-domain non-orthogonal technology in the fifth-generation mobile communication (5G), can be modulated by orthogonal frequency division multiplexing (OFDM) to improve the link quality of a single user. In this paper, a high-security SCMA-OFDM multi-core fiber transmission system based on a regular hexagonal chaotic codebook is proposed for next-generation passive optical network (PON). The whole encryption process consists of a regular hexagon chaotic codebook design and frequency domain block scrambling. In designing the regular hexagon chaotic codebook, the optimization of constellation points on orthogonal resources are considered as the starting point. Firstly, the chaos factor generated by the four-dimensional Rossler chaos model is deployed to disturb the mother constellation, and then the corresponding chaotic book is formed by rotating the mother constellation and multiplying the sparse matrix. The designed codebook logically avoids the degradation of transmission performance caused by the rough scrambling of codebook constellation, to find a balance between codebook disturbance and bit error rate (BER). The security and reliability of the transmission system have been verified by performing 42 Gb/s encrypted SCMA-OFDM data transmission experiments in a 2km multi-core fiber. The key space of the encryption scheme can reach 10178, which effectively ensures the security of the transmission system. Furthermore, the performance of the transmission system with a regular hexagon chaotic codebook is improved by 2.5 dB compared with the traditional codebook when the BER is 1 × 10-3. Moreover, the SCMA-OFDM-based transmission architecture and the detection effects of different multi-user detection algorithms in the SCMA-OFDM multi-core fiber transmission system are also studied.

Mode division multiplexing chaotic encryption scheme based on key intertwining and accompanying transmission.

A mode division multiplexing (MDM) chaotic encryption scheme based on key intertwining and accompanying transmission is proposed in this paper. Based on the weakly coupled few-mode fiber (FMF), data and time-varying keys can be accompanied by transmission in two modes, LP01 and LP11, respectively. In order to generate a new key, the current key is XORed with all of the keys from all the preceding moments, one by one. To implement chaotic masking in the digital domain, the three chaotic sequences corresponding to the new key are adopted to encrypt the data at the constellation phase, data symbol block, and subcarrier levels. An 8.89 Gb/s encrypted 16QAM-OFDM signal transmission over 1 km weakly-coupled FMF is experimentally demonstrated. The receiver with the correct key can recover the data normally, while the BER of the illegal receiver remains around 0.5. In the case of the key transmission bit rate of 1 Gb/s, the cracking efficiency threshold of the time-varying key encryption scheme is 5.21 × 106 times that of the time-invariant key encryption scheme, which suggests that the proposed work is a promising candidate for future physical layer security.

Protective effect of melatonin on alleviating early oxidative stress induced by DOX in mice spermatogenesis and sperm quality maintaining.

Doxorubicin (DOX) is an effective chemotherapy drug, but its clinical use has adverse effects on male reproduction. However, there are few studies about the specific biological processes related to male reproduction or strategies for improving fertility protection. In this paper, we examined the effects of DOX on spermatogenesis and sperm function, and tested the possible protective role of melatonin (MLT) against DOX's reproductive toxicity. DOX-treated mice showed signs of significantly impaired spermatogenesis, including vacuolated epithelial cells, decreased testis weights, and lowered sperm counts and motility. DOX also reduced germ cell proliferation (PCNA) and meiosis-related proteins (SYCP3), but this effect could be partially improved with MLT administration. HSPA2 expression was maintained, which indicated that although MLT did not improve sperm motility, it did have a significant protective effect on elongated sperm. IVF results showed that MLT could partially promote two-cell and blastocyte development that was restricted by DOX. MLT reversed DOX-driven changes in the testes, including the antioxidant indices of SOD1, CAT and PRDX6, and the apoptotic indices of BAX and Caspase3. These results suggest that MLT effectively prevents DOX-induced early reproductive toxicity, and increase our understanding of the molecular mechanisms underlying DOX's effects on male reproduction and the protective mechanism of MLT.

Transformer-Based Maneuvering Target Tracking.

When tracking maneuvering targets, recurrent neural networks (RNNs), especially long short-term memory (LSTM) networks, are widely applied to sequentially capture the motion states of targets from observations. However, LSTMs can only extract features of trajectories stepwise; thus, their modeling of maneuvering motion lacks globality. Meanwhile, trajectory datasets are often generated within a large, but fixed distance range. Therefore, the uncertainty of the initial position of targets increases the complexity of network training, and the fixed distance range reduces the generalization of the network to trajectories outside the dataset. In this study, we propose a transformer-based network (TBN) that consists of an encoder part (transformer layers) and a decoder part (one-dimensional convolutional layers), to track maneuvering targets. Assisted by the attention mechanism of the transformer network, the TBN can capture the long short-term dependencies of target states from a global perspective. Moreover, we propose a center-max normalization to reduce the complexity of TBN training and improve its generalization. The experimental results show that our proposed methods outperform the LSTM-based tracking network.

Supercritical Fluid Microcellular Foaming of High-Hardness TPU via a Pressure-Quenching Process: Restricted Foam Expansion Controlled by Matrix Modulus and Thermal Degradation.

High-hardness thermoplastic polyurethane (HD-TPU) presents a high matrix modulus, low-temperature durability, and remarkable abrasion resistance, and has been used in many advanced applications. However, the fabrication of microcellular HD-TPU foam is rarely reported in the literature. In this study, the foaming behavior of HD-TPU with a hardness of 75D was investigated via a pressure-quenching foaming process using CO2 as a blowing agent. Microcellular HD-TPU foam with a maximum expansion ratio of 3.9-fold, a cell size of 25.9 µm, and cell density of 7.8 × 108 cells/cm3 was prepared, where a high optimum foaming temperature of about 170 °C had to be applied with the aim of softening the polymer's matrix modulus. However, the foaming behavior of HD-TPU deteriorated when the foaming temperature further increased to 180 °C, characterized by the presence of coalesced cells, microcracks, and a high foam density of 1.0 g/cm3 even though the crystal domains still existed within the matrix. The cell morphology evolution of HD-TPU foam was investigated by adjusting the saturation time, and an obvious degradation occurred during the high-temperature saturation process. A cell growth mechanism of HD-TPU foams in degradation environments was proposed to explain this phenomenon based on the gas escape through the defective matrix.

Ruxolitinib mitigates steroid-refractory CRS during CAR T therapy.

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity are two major CAR T related toxicities. With the interventions of Tocilizumab and steroids, many patients can recover from severe CRS. However, some patients are refractory to steroids and develop life-threatening consequences. Ruxolitinib is an oral JAKs inhibitor and promising drug in inflammatory diseases. In this pilot study, we evaluate the efficacy of Ruxolitinib in CRS. Of 14 r/r B-ALL children who received CD19 or CD22 CAR T cell therapies, 4 patients developed severe (≥grade 3) CRS with symptoms that were not alleviated with high-dose steroids and thus received ruxolitinib. Rapid resolution of CRS symptoms was observed in 4 patients after ruxolitinib treatment. Serum cytokines significantly decreased after ruxolitinib intervention. All patients achieved complete remission on day 30 after infusion, and we could still detect CAR T expansion in vivo despite usage of ruxolitinib. There were no obvious adverse events related to ruxolitinib. In vitro assays revealed that ruxolitinib could dampen CAR T expansion and cytotoxicity, suggesting that the timing and dosage of ruxolitinib should be carefully considered to avoid dampening anti-leukaemia response. Our results suggest that ruxolitinib is active and well tolerated in steroid-refractory and even life-threatening CRS.

Toxicity and effectiveness of CD19 CAR T therapy in children with high-burden central nervous system refractory B-ALL.

INTRODUCTION: Although recent clinical trials have demonstrated the efficacy of CD19-directed chimeric antigen receptor (CAR) T-cell therapy for refractory or relapsed B acute lymphoblastic leukemia (r/r B-ALL), most trials exclude patients with high-burden CNS leukemia (CNSL) to avoid the risk of severe neurotoxicity. There were only sparse cases describing the effect of CAR T cells on low-burden CNSL, and the safety and effectiveness of CAR T cells in high-burden CNSL remains unknown. METHODS: Here, we retrospectively analyzed the results of CD19 CAR T-cell therapy in 12 pediatric patients that had low (Blasts < 20/µL in CSF) or high-burdens (Blasts or intracranial solid mass) of CNS B-ALL, that are enrolled in three clinical trials and one pilot study at Beijing Boren Hospital RESULTS: Eleven patients (91.7%) achieved complete remission (CR) on day 30, and one patient got CR on day 90 after infusion. Most patient experienced mild cytokine-release syndrome. However, of the five patients who retained > 5/µL blasts in CSF or a solid mass before CAR T-cell expansion, four developed severe (grade 3-4) neurotoxicity featured by persistent cerebral edema and seizure, and they fully recovered after intensive managements. Sustained remission was achieved in 9 of the 12 patients, resulted in a 6-month leukemia-free survival rate of 81.8% (95% CI 59.0-100). Only one patient has CNS relapse again. CONCLUSION: Our study demonstrates that CAR T cells are effective in clearing both low- and high-burden CNSL, but a high CNSL burden before CAR T-cell expansion may cause severe neurotoxicity requiring intense intervention.

An LTR retrotransposon-derived lncRNA interacts with RNF169 to promote homologous recombination.

LTR retrotransposons are abundant repetitive elements in the human genome, but their functions remain poorly understood. Here, we report the function and regulatory mechanism of an ERV-9 LTR retrotransposon-derived lncRNA called p53-regulated lncRNA for homologous recombination (HR) repair 1 (PRLH1) in human cells. PRLH1 is highly expressed in p53-mutated hepatocellular carcinoma (HCC) samples and promotes cell proliferation in p53-mutated HCC cells, and its transcription is promoted by NF-Y and suppressed by p53. Mechanistically, PRLH1 specifically binds to an uncharacterized domain of RNF169 through two GCUUCA boxes in its 5' terminal region to form a DNA repair complex that supplants 53BP1 at double-strand break (DSB) sites and then promotes the initiation of HR repair. Notably, PRLH1 is essential for the stabilization of RNF169, acting as an RNA platform to recruit and assemble HR protein factors. This study characterizes PRLH1 as a novel HR-promoting factor and provides new insights into the function and mechanism of LTR retrotransposon-derived lncRNAs.

A panel of extracellular vesicle long noncoding RNAs in seminal plasma for predicting testicular spermatozoa in nonobstructive azoospermia patients.

STUDY QUESTION: Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients? SUMMARY ANSWER: Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA. WHAT IS KNOWN ALREADY: The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE. STUDY DESIGN, SIZE, DURATION: RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets. MAIN RESULTS AND THE ROLE OF CHANCE: A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended. LIMITATIONS, REASONS FOR CAUTION: In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated. WIDER IMPLICATIONS OF THE FINDINGS: When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study. TRIAL REGISTRATION NUMBER: N/A.

dreamBase: DNA modification, RNA regulation and protein binding of expressed pseudogenes in human health and disease.

Although thousands of pseudogenes have been annotated in the human genome, their transcriptional regulation, expression profiles and functional mechanisms are largely unknown. In this study, we developed dreamBase (http://rna.sysu.edu.cn/dreamBase) to facilitate the investigation of DNA modification, RNA regulation and protein binding of potential expressed pseudogenes from multidimensional high-throughput sequencing data. Based on ∼5500 ChIP-seq and DNase-seq datasets, we identified genome-wide binding profiles of various transcription-associated factors around pseudogene loci. By integrating ∼18 000 RNA-seq data, we analysed the expression profiles of pseudogenes and explored their co-expression patterns with their parent genes in 32 cancers and 31 normal tissues. By combining microRNA binding sites, we demonstrated complex post-transcriptional regulation networks involving 275 microRNAs and 1201 pseudogenes. We generated ceRNA networks to illustrate the crosstalk between pseudogenes and their parent genes through competitive binding of microRNAs. In addition, we studied transcriptome-wide interactions between RNA binding proteins (RBPs) and pseudogenes based on 458 CLIP-seq datasets. In conjunction with epitranscriptome sequencing data, we also mapped 1039 RNA modification sites onto 635 pseudogenes. This database will provide insights into the transcriptional regulation, expression, functions and mechanisms of pseudogenes as well as their roles in biological processes and diseases.

Spatial-temporal transcriptional dynamics of long non-coding RNAs in human brain.

The functional architecture of the human brain is greatly determined by the temporal and spatial regulation of the transcription process. However, the spatial and temporal transcriptional landscape of long non-coding RNAs (lncRNAs) during human brain development remains poorly understood. Here, we report the genome-wide lncRNA transcriptional analysis in an extensive series of 1340 post-mortem human brain specimens collected from 16 regions spanning the period from early embryo development to late adulthood. We discovered that lncRNA transcriptome dramatically changed during fetal development, while transited to a surprisingly relatively stable state after birth till the late adulthood. We also discovered that the transcription map of lncRNAs was spatially different, and that this spatial difference was developmentally regulated. Of the 16 brain regions explored (cerebellar cortex, thalamus, striatum, amygdala, hippocampus and 11 neocortex areas), cerebellar cortex showed the most distinct lncRNA expression features from all remaining brain regions throughout the whole developmental period, reflecting its unique developmental and functional features. Furthermore, by characterizing the functional modules and cellular processes of the spatial-temporal dynamic lncRNAs, we found that they were significantly associated with the RNA processing, neuron differentiation and synaptic signal transportation processes. Furthermore, we found that many lncRNAs associated with the neurodegenerative Alzheimer and Parkinson diseases were co-expressed in the fetal development of the human brain, and affected the convergent biological processes. In summary, our study provides a comprehensive map for lncRNA transcription dynamics in human brain development, which might shed light on the understanding of the molecular underpinnings of human brain function and disease.

Coexistence and Sudden Entrapment between Two Dissimilar, Miscible Oil Lenses.

The property of substrates is one of the important factors determining the interaction between two lenses (droplets). There likely exist different interactions between two dissimilar oil lenses (droplets) floating on the surface of a liquid phase from the interaction between two dissimilar oil droplets on a rigid substrate, for example, coalescence or coexistence. The interaction between two dissimilar oil lenses (droplets) is dependent on the intrinsic properties of both oil lenses (droplets) and external environmental factors. In this work, we investigate the contact interaction between two dissimilar, miscible oil lenses (toluene and silicone oil) on the surface of deionized water (DI water). The morphological evolution of two dissimilar, miscible oil lenses during the interaction under different experimental conditions is recorded and analyzed. The effects of the volume ratio of two dissimilar, miscible oil lenses, temperature of DI water, and viscosity of silicone oil on characteristic parameters are systematically studied. A sudden "entrapment" of a toluene lens into a silicone oil lens occurs after a period of the "mass exchange" (coexistence) between these two oil lenses. Several characteristic parameters, including the duration of the "mass exchange" and critical sizes of the toluene lens at the onset of the entrapment and after the entrapment, are found to be dependent on experimental conditions.