A kinetic model for solving a combination optimization problem in ab-initio Cryo-EM 3D reconstruction.

Cryo-Electron Microscopy (cryo-EM) is a widely used and effective method for determining the three-dimensional (3D) structure of biological molecules. For ab-initio Cryo-EM 3D reconstruction using single particle analysis (SPA), estimating the projection direction of the projection image is a crucial step. However, the existing SPA methods based on common lines are sensitive to noise. The error in common line detection will lead to a poor estimation of the projection directions and thus may greatly affect the final reconstruction results. To improve the reconstruction results, multiple candidate common lines are estimated for each pair of projection images. The key problem then becomes a combination optimization problem of selecting consistent common lines from multiple candidates. To solve the problem efficiently, a physics-inspired method based on a kinetic model is proposed in this work. More specifically, hypothetical attractive forces between each pair of candidate common lines are used to calculate a hypothetical torque exerted on each projection image in the 3D reconstruction space, and the rotation under the hypothetical torque is used to optimize the projection direction estimation of the projection image. This way, the consistent common lines along with the projection directions can be found directly without enumeration of all the combinations of the multiple candidate common lines. Compared with the traditional methods, the proposed method is shown to be able to produce more accurate 3D reconstruction results from high noise projection images. Besides the practical value, the proposed method also serves as a good reference for solving similar combinatorial optimization problems.

Socioeconomic changes predict genome-wide DNA methylation in childhood.

Childhood socioeconomic position (SEP) is a major determinant of health and well-being across the entire life course. To effectively prevent and reduce health risks related to SEP, it is critical to better understand when and under what circumstances socioeconomic adversity shapes biological processes. DNA methylation (DNAm) is one such mechanism for how early life adversity 'gets under the skin'. In this study, we evaluated the dynamic relationship between SEP and DNAm across childhood using data from 946 mother-child pairs in the Avon Longitudinal Study of Parents and Children. We assessed six SEP indicators spanning financial, occupational and residential domains during very early childhood (ages 0-2), early childhood (ages 3-5) and middle childhood (ages 6-7). Epigenome-wide DNAm was measured at 412 956 cytosine-guanines (CpGs) from peripheral blood at age 7. Using an innovative two-stage structured life-course modeling approach, we tested three life-course hypotheses for how SEP shapes DNAm profiles-accumulation, sensitive period and mobility. We showed that changes in the socioeconomic environment were associated with the greatest differences in DNAm, and that middle childhood may be a potential sensitive period when socioeconomic instability is especially important in shaping DNAm. Top SEP-related DNAm CpGs were overrepresented in genes involved in pathways important for neural development, immune function and metabolic processes. Our findings highlight the importance of socioeconomic stability during childhood and if replicated, may emphasize the need for public programs to help children and families experiencing socioeconomic instability and other forms of socioeconomic adversity.

Delta-sigma modulation supporting the 4194304QAM dual polarization signal at the W-band transmission over a 4.6†km wireless distance.

In this Letter, we propose a dual-polarized coherent millimeter-wave system based on differential delta-sigma modulation (D-DSM) intended for long-distance wireless transmission in the W-band. The proposed system can transmit polarization-division-multiplexed (PDM) D-DSM signals with modulation orders up to 4194304QAM over a wireless channel for 4.6 km at a signal baud rate of 20 G. After 4.6 km of wireless transmission, we successfully achieve a bit error rate (BER) lower than the hard-decision forward error correction (HD-FEC) of 3.8 × 10-3 for 34.51 Gbit/s PDM-524288QAM and a BER lower than the soft-decision forward error correction (SD-FEC) of 4.2 × 10-2 for 32.23 Gbit/s PDM-4194304QAM.

Strategies for the Construction of Benzobicyclo[3.2.1]octane in Natural Product Synthesis.

Benzobicyclo[3.2.1]octane is a cage-like unique motif containing a bicyclo[3.2.1]octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo[3.2.1]octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework.

Post-traumatic stress disorder symptom remission and cognition in a large cohort of civilian women.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit. METHODS: Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively. RESULTS: Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression. CONCLUSION: Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Dynamic network reorganization underlying neuroplasticity: the deficits-severity-related language network dynamics in patients with left hemispheric gliomas involving language network.

Brain network dynamics not only endow the brain with flexible coordination for various cognitive processes but also with a huge potential of neuroplasticity for development, skill learning, and after cerebral injury. Diffusive and progressive glioma infiltration triggers the neuroplasticity for functional compensation, which is an outstanding pathophysiological model for the investigation of network reorganization underlying neuroplasticity. In this study, we employed dynamic conditional correlation to construct framewise language networks and investigated dynamic reorganizations in 83 patients with left hemispheric gliomas involving language networks (40 patients without aphasia and 43 patients with aphasia). We found that, in healthy controls (HCs) and patients, the language network dynamics in resting state clustered into 4 temporal-reoccurring states. Language deficits-severity-dependent topological abnormalities of dFCs were observed. Compared with HCs, suboptimal language network dynamics were observed for those patients without aphasia, while more severe network disruptions were observed for those patients with aphasia. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the 4 states significantly predicted individual patients' language scores. These findings shed light on our understanding of metaplasticity in glioma. Glioma-induced language network reorganizations were investigated under a dynamic "meta-networking" (network of networks) framework. In healthy controls and patients with glioma, the framewise language network dynamics in resting-state robustly clustered into 4 temporal-reoccurring states. The spatial but not temporal language deficits-severity-dependent abnormalities of dFCs were observed in patients with left hemispheric gliomas involving language network. Language network dynamics significantly predicted individual patients' language scores.

The domain-separation language network dynamics in resting state support its flexible functional segregation and integration during language and speech processing.

Modern linguistic theories and network science propose that language and speech processing are organized into hierarchical, segregated large-scale subnetworks, with a core of dorsal (phonological) stream and ventral (semantic) stream. The two streams are asymmetrically recruited in receptive and expressive language or speech tasks, which showed flexible functional segregation and integration. We hypothesized that the functional segregation of the two streams was supported by the underlying network segregation. A dynamic conditional correlation approach was employed to construct framewise time-varying language networks and k-means clustering was employed to investigate the temporal-reoccurring patterns. We found that the framewise language network dynamics in resting state were robustly clustered into four states, which dynamically reconfigured following a domain-separation manner. Spatially, the hub distributions of the first three states highly resembled the neurobiology of speech perception and lexical-phonological processing, speech production, and semantic processing, respectively. The fourth state was characterized by the weakest functional connectivity and was regarded as a baseline state. Temporally, the first three states appeared exclusively in limited time bins (∼15%), and most of the time (> 55%), state 4 was dominant. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the four states significantly predicted individual linguistic performance. These findings suggest a domain-separation manner of language network dynamics in resting state, which forms a dynamic "meta-network" framework to support flexible functional segregation and integration during language and speech processing.

The trichotomy of HER2 expression confers new insights into the understanding and managing for breast cancer stratified by HER2 status.

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that plays a carcinogenic role in breast cancer (BC) through gene amplification, mutation, or overexpression. Traditional methods of HER2 detection were divided into positive (immunohistochemistry (IHC) 3+/fluorescence in situ hybridization (FISH) amplification) and negative (IHC 2+/FISH-, IHC 1+, IHC 0) according to the dichotomy method. Anti-HER2-targeted therapies, such as trastuzumab and pertuzumab, have significantly improved the prognosis of HER2-positive patients. However, up to 75% to 85% of patients remain HER2-negative. In recent years, with the rapid development of molecular biology, gene detection technology, targeted therapy, and immunotherapy, researchers have actively explored the clinicopathological characteristics, molecular biological characteristics, treatment methods, and HER2 detection methods of HER2-low/zero breast cancer. With the clinical efficacy of new anti-HER2 targeted drugs, accurate classification of breast cancer is very important for the treatment choice. Therefore, the following review summarizes the necessity of developing HER2 detection methods, and the clinicopathological and drug treatment characteristics of patients with HER2-low/zero, to light the dawn of the treatment of breast cancer patients with HER2-low/zero expression.

Real-time demonstration of a low-complexity PS scheme for 16QAM-DMT signals in an IM-DD system.

We experimentally demonstrated a low-complexity probabilistic shaping (PS) 16-ary quadrature amplitude modulation (16QAM) scheme based on intra-symbol bit-weighted distribution matching (Intra-SBWDM) for discrete multi-tone (DMT) symbols with field-programmable gate array implementation in an intensity modulation and direct detection (IM-DD) system. Different from the traditional PS scheme such as Gallager many-to-one mapping, hierarchical distribution matching and constant composition distribution matching, the Intra-SBWDM scheme with lower computation and hardware complexity does not need to continuously refine the interval to find the target symbol probability, nor does it need a look-up table, so it does not introduce a large number of extra redundant bits. In our experiment, four PS parameter values (k = 4, 5, 6, and 7) are investigated in a real-time short-reach IM-DD system. 31.87-Gbit/s net bit PS-16QAM-DMT (k = 4) signal transmission is achieved. The results show that the receiver sensitivity in terms of the received optical power of the real-time PS scheme based on Intra-SBWDM (k = 4) over OBTB/20 km standard single-mode fiber can be improved by about 1.8/2.2 dB at the bit error rate (BER) of 3.8 × 10-3, compared to the uniformly-distributed DMT. In addition, the BER is steadily lower than 3.8 × 10-3 during a one-hour measurement for PS-DMT transmission system.

PDM-OFDM 1-bit DSM 1024QAM/4096QAM signals at W-band transmission over 4.6-km wireless distance.

In this Letter, we propose the application of delta-sigma modulation (DSM) higher-order quadrature amplitude modulation (QAM) technology in long-distance transmission of W-band wireless communication, and demonstrate, for the first time to the best of our knowledge, the wireless transmission of millimeter wave signals in the W-band based on 1-bit DSM quantization using polarization-division-multiplexed orthogonal frequency division multiplexing (PDM-OFDM) 1024QAM/4096QAM for 4.6 km. We successfully achieved a bit error rate (BER) of 40-Gbit/s PDM-OFDM 1024QAM and 48-Gbit/s PDM-OFDM 4096QAM after 4.6-km wireless transmission, both lower than the soft decision forward error correction (SD-FEC) of 4.2 × 10-2. To the best of our knowledge, this is the first time that up to 4096QAM signals have been quantized and transmitted based on 1-bit DSM in a 4.6-km-long distance W-band millimeter wave system.

W-band RoF polarization multiplexing system supports 1048576 QAM with delta-sigma modulation.

We propose and experimentally verify a photonics-aided W-band millimeter wave (MMW) radio-over-fiber (RoF) polarization-multiplexed envelope detection system for high-order quadrature amplitude modulation (QAM) signals. To solve the problem of low spectral efficiency of common public radio interface (CPRI) and severe distortion of high-order QAM of envelope detection, quantization noise suppressed delta-sigma modulation (DSM) is introduced into the system. The experimental results show that the system can transmit 131072 QAM signals when meeting the error vector magnitude (EVM) requirements of 5G new radio (NR), and transmit 1048576 QAM signals when meeting the soft decision threshold (SD@20%).

High quality stealth dicing of sapphire with a picosecond Bessel beam by controlling the polarization direction.

Sapphire is an important substrate material in optoelectronic devices, and it is also widely used as a touch screen panel. In order to achieve high quality cutting of sapphire, the stealth dicing of 500 µm thick sapphire by a picosecond Bessel beam is studied in this paper. The influences of laser polarization direction and process parameters on cutting section roughness were studied. By controlling the laser polarization direction, different crack propagation morphologies were obtained. When the polarization direction was vertical to the cutting path, the crack propagation path was straighter, and the sapphire had better cutting quality. The laser processing parameters, including burst mode, hole spacing, and pulse energy, had a significant impact on the cutting section roughness. When the polarization direction was vertical to the cutting path under the optimal process parameters, the cutting section was uniform and flat, with no recondensable particles, no ripples, and no chamfer, and an 89.7 nm average roughness of the cutting section could be obtained.

The over-expression of miRNA-206 in peripheral blood of patients with burning mouth syndrome and its relationship with anxiety and depression.

BACKGROUND: Burning mouth syndrome (BMS) is characterised by persisting burning pain of the oral mucosa, and its etiopathogenesis remains poorly understood. OBJECTIVES: Our study aimed to detect the expression of miRNA-206 in the blood and clarify the relationship among miRNA-206, pain, anxiety and depression of BMS patients. METHODS: Thirty patients with BMS and 30 healthy individuals were enrolled in the experimental and control groups, respectively. Data on medical history and clinical oral examination for all participants were collected. Simultaneously, scores of Visual Analogous Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were administered. The expression level of miRNA-206 in plasma were determined by RT-(q)PCR. Finally, the relationship of miRNA-206 expression with the VAS score, SAS score, and SDS score was analysed. Chi-square test and t-test were used for statistical analysis of the data, and p < .05 was considered statistically significant. RESULTS: The majority of the patients with BMS identified the tongue as the main pain area, and showed dry mouth and poor sleep quality. The SAS and SDS scores of patients with BMS were higher than those of healthy controls (p < .05) and were positively correlated with VAS pain score. In addition, miRNA-206 expression was higher in patients with BMS than in healthy individuals (p < .05), and was positively correlated with the VAS and SDS scores (p < .05). CONCLUSIONS: Patients with BMS suffer from pain and tend to be more anxious and depressed than healthy controls. miRNA-206 expression in the peripheral blood of patients with BMS is positively correlated with pain and depression, which may be involved in the pathogenesis of BMS.

CircEpha5 regulates the synthesis and secretion of androgen in mouse preantral follicles by targeting miR-758-5p.

Circular RNAs are involved in the pathogenesis of various diseases, although its expression pattern and role in polycystic ovary syndrome (PCOS), characterised by hyperandrogenism, are not very clear. This article assessed the circRNAs expression profile in the ovaries of PCOS mice by circRNAs high-throughput sequencing and explored the role of circEpha5 in hyperandrogenism. The results showed that the overexpression of circEpha5 in mouse preantral follicles could increase the expression of Cyp17a1, an androgen synthesis-related gene, which resulted in a higher serum level of testosterone. Dual-luciferase reporter gene studies identified miR-758-5p as a direct target of circEpha5. Consequently, miR-758-5p expression was downregulated upon circEpha5 overexpression. Ectopically expressed miR-758-5p reversed the stimulation effects of circEpha5 on steroidogenesis-related gene expression and testosterone release. Therefore, circEpha5 could sponge miR-758-5p to regulate the expression of Cyp17a1, thereby promoting the synthesis and secretion of androgen in the preantral follicles. This work is contributed to the understanding of the pathogenesis of hyperandrogenemia and lays the foundation for the development of therapeutic targets of PCOS hyperandrogenism.

IMPACT STATEMENTWhat is already known on this subject? PCOS is a complex endocrine and metabolic disorders with hyperandrogenism as the main clinical manifestation. There are a variety of abnormal expression circRNAs in PCOS, however, the relationship between circEpha5 and hyperandrogenism has yet to be fully elucidated.What do the results of this study add? We first found that expression levels of serum circEpha5 were significantly higher in PCOS than in a normal group. Using mouse preantral follicle culture model and the letrozole-induced PCOS mouse model, the mechanism of CircEpha5 regulating androgen secretion was studied.What the implications are of these findings for clinical practice and/or further research? It was revealed that CircEpha5 can absorb miR-758-5p in the sponge to regulate the expression of Cyp17a1, thereby promoting the synthesis and secretion of androgen in preantral follicles, which may become a key target for the screening and treatment of PCOS hyperandrogenism.

Asymmetric Total Synthesis of Naphthospironone A.

Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesised for the first time in this study. The spiro[bicyclo[3.2.1]octane-pyran] core was constructed by an acid-promoted epoxide-opening lactonisation and a base-induced intramolecular aldol-type cyclisation.

Joint communication and radar sensing functions system based on photonics at the W-band.

The photonics-based technology has the advantages of wide bandwidth in millimeter wave (mm-wave) communication and radar sensing systems. In the present work, we propose a novel joint communication and radar sensing functions system based on photonics at the W-band. In the proposed system, the broadband linear frequency modulated (LFM) signal and high-speed M-quadrature amplitude modulation (MQAM) signal are simultaneously obtained by heterodyning two free-running external cavity lasers (ECLs). Based on this system, a communication rate of 78 Gbit/s and a radar with a 5-GHz bandwidth is achieved. This is a good solution to incorporate a high-speed communication and high-resolution radar sensing functions system.

THz-over-fiber transmission with a net rate of 5.12 Tbps in an 80 channel WDM system.

An experimental demonstration of the ultra-large-capacity terahertz (THz)-wave signal transmission over a 20-km wired and 54-m wireless distance in an 80-channel wavelength division multiplexing (WDM) system is successfully realized for the first time, to the best of our knowledge. Based on optical asymmetric single-sideband (ASSB) modulation and advanced digital signal processing (DSP) algorithms, we achieve a record line rate of 6.4 Tbit/s (net rate of 5.12 Tbit/s) in a THz-over-fiber communication system. This experimental demonstration can provide an effective solution for ultra-large-capacity THz-over-fiber communication in future 6G networks.

The association of posttraumatic stress disorder, depression, and head injury with mid-life cognitive function in civilian women.

BACKGROUND: Despite evidence linking posttraumatic stress disorder (PTSD), depression, and head injury, separately, with worse cognitive performance, investigations of their combined effects on cognition are limited in civilian women. METHODS: The Cogstate Brief Battery assessment was administered in 10,681 women from the Nurses' Health Study II cohort, mean age 64.9 years (SD = 4.6). Psychological trauma, PTSD, depression, and head injury were assessed using online questionnaires. In this cross-sectional analysis, we used linear regression models to estimate mean differences in cognition by PTSD/depression status and stratified by history of head injury. RESULTS: History of head injury was prevalent (36%), and significantly more prevalent among women with PTSD and depression (57% of women with PTSD and depression, 21% of women with no psychological trauma or depression). Compared to having no psychological trauma or depression, having combined PTSD and depression was associated with worse performance on psychomotor speed/attention ( ß = -.15, p = .001) and learning/working memory ( ß = -.15, p < .001). The joint association of PTSD and depression on worse cognitive function was strongest among women with past head injury, particularly among those with multiple head injuries. CONCLUSIONS: Head injury, like PTSD and depression, was highly prevalent in this sample of civilian women. In combination, these factors were associated with poorer performance on cognitive tasks, a possible marker of future cognitive health. Head injury should be further explored in future studies of PTSD, depression and cognition in women.

Adverse Event Profile for Nanoparticle Albumin-Bound Paclitaxel Compared With Solvent-Based Taxanes in Solid-Organ Tumors: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an innovative form of taxane that has superior antitumor effects; however, the safety profile between nab-paclitaxel and traditional taxanes remains controversial. OBJECTIVE: To determine the burden of adverse events (AEs) in patients with multiple malignancies receiving nab-paclitaxel compared with that in patients receiving traditional taxanes. METHODS: Randomized clinical trials comparing nab-paclitaxel with traditional taxanes (solvent-based paclitaxel [sb-paclitaxel] or docetaxel) in the treatment of primary solid-organ malignancies were included if AEs were reported as an outcome. Statistical analyses were conducted to calculate the summary odds ratio (OR) of the relevant adverse outcomes related to nab-paclitaxel and traditional taxanes. Prespecified subgroup analyses based on intervention and doses, primary tumor sites, and different ethnic groups were also performed. RESULTS: Twelve clinical trials were included in the meta-analysis. Grade 3/4 anemia, thrombocytopenia, and neurotoxicity were more frequent with nab-paclitaxel than with traditional taxanes. Nab-paclitaxel at 100 or 125 mg/m2/w dosage was associated with fewer or similar grade 3/4 specific AEs. Allergy was less common with nab-paclitaxel. The median recovery times of neurotoxicity were 25, 64, and 37 days in patients receiving nab-paclitaxel, sb-paclitaxel, and docetaxel, respectively. Elevated incidences of specific AEs were more common in breast cancer and non-Asian patients than in other malignancies and ethnic groups, respectively. CONCLUSION AND RELEVANCE: Nab-paclitaxel increased the risk of hematologic and non-hematologic AEs in general, but anaphylaxis was less common, and the recovery duration of neurotoxicity was shorter. Weekly administration of nab-paclitaxel at a lower dosage provided better tolerance.

Effect of probiotics on gingival inflammation and oral microbiota: A meta-analysis.

To evaluate the effect of probiotics on gingival inflammation and oral microbiota in patients suffering from plaque-induced gingivitis. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were electronically searched until December 2020. The quality of included studies was assessed with the Cochrane Collaboration's Risk of Bias tool. The differences were expressed as weighted mean differences (WMD) and 95% of confidence interval (95% CI). I2 test was performed to evaluate the heterogeneity of the studies. All analyses were performed using Review Manager (version 5.3). Eleven randomized and controlled trials were included, enrolling 554 patients. All comparisons displayed that oral probiotics had no significant improvement in the Gingival Index (GI), Plaque Index (PI), and bleeding on probing (BOP) of patients with plaque-induced gingivitis. In terms of microecology, no significant difference in the volumes of gingival crevicular fluid (GCF), the concentration of IL-1ß, and the counts of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), and Fusobacterium nucleatum (Fn) were found between the probiotic group and the placebo group. There exists no clear evidence that oral probiotics have positive effect on gingival inflammation and oral microecological environment of patients with plaque-induced gingivitis.