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في هذا الكتاب الحصن المحاصر للمؤلف تشيان جونغ شو يتحدث ويتناول المؤلف عن حصار المجتمع الصيني وبالأخص طبقة المثقفين في تلك الفترة داخل أنفسها قبل أن يكون حصارا بأسوار الاحتلال وكما تناول غلبة الصراع من النزاع الداخلي والتزاحم في جو من المكائد بدلا من التركيز في مواجهة العدو الياباني المشترك في هذا الوقت.

In this work, we propose a scheme for cosmic evolution in a generalized Rastall gravity. In our approach, the role of dark energy is taken by the non-conserved sector of the stress energy–momentum tensor. The resultant cosmic evolution is found to naturally consists of three stages, namely, radiation dominated, ordinary matter dominated, as well as dark energy and dark matter dominated eras. Furthermore, for the present model, it is demonstrated that the eventual fate of the Universe is mostly insensitive to the initial conditions, in contrast to the standard Λ CDM model. In particular, the solution displays the properties of a dynamic attractor, which is reminiscent of quintessence and k-essence models. Subsequently, the cosmic coincidence problem is averted. The amount of deviation from a conserved stress energy–momentum tensor is shown to be more remarkable during the period when the dark energy evolves more rapidly. On the other hand, the conservation law is largely restored for the infinite past and future. The implications of the present approach are addressed.

Background The study aimed to appraise the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in amyotrophic lateral sclerosis (ALS), and to explore the associations between non-motor symptoms (mood changes, cognitive disturbances and sleep disturbances). Methods EQ-5D-5L descriptive scores were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ-VAS) was used for self-rating of current health status. Multiple logistic regression analysis was used to explore the factors associated with HRQoL. Results Among the 547 enrolled ALS patients who were assessed using EQ-5D-5L, the highest frequency of reported problems was with usual activities (76.7%), followed by self-care (68.8%) and anxiety/depression (62.0%). The median health utility score was 0.78 and the median EQ-VAS score was 70. Clinical factors corresponding to differences in the EQ-5D-5L health utility score included age of onset, onset region, the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and King’s College stages. Patients with depression, anxiety, and poor sleep had lower health utility scores. Patients with excessive daytime sleepiness and rapid eye movement sleep behavior disorder had lower EQ-VAS scores. Multivariate logistic analysis indicated that ALSFRS-R scores, depression, and anxiety were associated with health utility scores. After adjusting other parameters, ALSFRS-R score, stages, and depression were significantly associated with EQ-VAS scores ( P  < 0.05). Conclusion This study examined HRQoL in ALS patients using the Chinese version of the EQ-5D-5L scale across different stages of the disease. We found that HRQoL is related to disease severity and to mood disturbances. Management of non-motor symptoms may help improve HRQoL in ALS patients.

Some nonprofits easily attract resources, while others struggle to survive. However, little is known about what characteristics account for the difference in nonprofit organizations’ capacity to mobilize resources, especially in authoritarian countries. Using multilevel modeling techniques and a national sample of 3344 philanthropic foundations in 31 regions of mainland China, this research seeks to address this knowledge gap by examining the effect of both organizational and contextual factors on foundations’ revenues, paying special attention to the government’s role. Results show that the distribution of resources is highly unbalanced in China’s foundation sector and that foundations with particular characteristics are systematically favored. By exploring what factors give foundations the edge in mobilizing resources, this study reveals how the Chinese government has used a more sophisticated, indirect method than direct control to shape resource distribution and regulate the development of nonprofits. Social organizations can survive and even thrive, but only certain types. Des organismes sans but lucratif parviennent aisément à attirer des ressources tandis que d’autres peinent à survivre. Nous en savons toutefois très peu sur les caractéristiques qui permettent aux organismes de mobiliser de telles ressources, surtout dans les pays autoritaires. À l’aide de techniques de modélisation à niveau multiple et d’un échantillon national de 3344 fondations philanthropiques de 31 régions du continent chinois, la présente recherche tente d’étudier cette carence en examinant l’effet que des facteurs organisationnels et contextuels ont sur les revenus desdites fondations, et ce, en se penchant particulièrement sur le rôle du gouvernement. Les résultats démontrent que la répartition des ressources est fortement déséquilibrée dans le secteur des fondations chinoises et que les fondations qui présentent des caractéristiques données sont systématiquement favorisées. En révélant les facteurs qui permettent aux fondations de mobiliser des ressources avant les autres, la présente étude décrit comment le gouvernement chinois a exercé un contrôle indirect, au lieu de s’impliquer directement, pour orienter la répartition et gouverner le développement des organismes sans but lucratif. Seuls les organismes sociaux de types donnés peuvent survivre, voire s’épanouir. Einige gemeinnützige Organisationen finden leichten Zugang zu Ressourcen, während andere ums Überleben kämpfen. Allerdings ist nur wenig darüber bekannt, welche Merkmale die unterschiedlichen Fähigkeiten der gemeinnützigen Organisationen zur Ressourcenmobilisierung erklären, insbesondere in autoritären Ländern. Anhand mehrstufiger Modellbildungsverfahren und einer landesweiten Stichprobe von 3.344 philantropischen Stiftungen aus 31 Regionen in Festlandchina möchte die vorliegende Studie diese Wissenslücke ansprechen, indem die Auswirkungen von sowohl organisatorischen als auch von kontextabhängigen Faktoren auf die Einnahmen der Stiftungen untersucht werden, wobei insbesondere die Rolle der Regierung berücksichtigt wird. Die Ergebnisse zeigen, dass die Ressourcenverteilung in Chinas Stiftungssektor äußerst unausgewogen ist und Stiftungen mit bestimmten Merkmalen systematisch bevorzugt werden. Die Studie deckt die Faktoren auf, welche Stiftungen einen Vorteil bei der Ressourcenmobilisierung verschaffen, und enthüllt so, wie die chinesische Regierung indirekt Kontrolle ausübt, statt direkt involviert zu sein, um die Ressourcenverteilung zu beeinflussen und die Entwicklung der gemeinnützigen Organisationen zu regulieren. Soziale Organisationen können überleben und sogar florieren, aber eben nur bestimmte. Algunas organizaciones sin ánimo de lucro atraen recursos fácilmente mientras que otras luchan por sobrevivir. Sin embargo, se sabe poco sobre qué características explican la diferencia en la capacidad de las organizaciones sin ánimo de lucro para movilizar recursos, especialmente en países autoritarios. Utilizando técnicas de modelado multinivel y una muestra nacional de 3344 fundaciones filantrópicas en 31 regiones de la China continental, la presente investigación trata de abordar esta brecha en el conocimiento examinando el efecto tanto de los factores organizativos como de los factores contextuales en los ingresos de las fundaciones, prestando especial atención al papel del gobierno. Los resultados muestran que la distribución de recursos está sumamente desequilibrada en el sector de las fundaciones de China y que las fundaciones con características específicas son favorecidas de manera sistemática. Mediante la revelación de qué factores dan ventaja a las fundaciones en la movilización de recursos, el presente estudio revela cómo el gobierno chino ha utilizado un control indirecto, en lugar de una implicación directa, para dar forma a la distribución de recursos y regular el desarrollo de las organizaciones sin ánimo de lucro. Las organizaciones sociales pueden sobrevivir e incluso desarrollarse, pero sólo determinados tipos.

A new analytical wake model for wind turbines, considering ambient turbulence intensity, thrust coefficient and yaw angle effects, is proposed from numerical and analytical studies. First, eight simulations by the Reynolds Stress Model are conducted for different thrust coefficients, yaw angles and ambient turbulence intensities. The wake deflection, mean velocity and turbulence intensity in the wakes are systematically investigated. A new wake deflection model is then proposed to analytically predict the wake center trajectory in the yawed condition. Finally, the effects of yaw angle are incorporated in the Gaussian-based wake model. The wake deflection, velocity deficit and added turbulence intensity in the wake predicted by the proposed model show good agreement with the numerical results. The model parameters are determined as the function of ambient turbulence intensity and thrust coefficient, which enables the model to have good applicability under various conditions.

Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1–GluA4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single-particle cryo–electron microscopy (cryo-EM). We find that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand-binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels. Methods Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients. Results Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection. Conclusions PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.

The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody‒drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future.

Nanoscale or single-cell technologies are critical for biomedical applications. However, current mass spectrometry (MS)-based proteomic approaches require samples comprising a minimum of thousands of cells to provide in-depth profiling. Here, we report the development of a nanoPOTS (nanodroplet processing in one pot for trace samples) platform for small cell population proteomics analysis. NanoPOTS enhances the efficiency and recovery of sample processing by downscaling processing volumes to <200 nL to minimize surface losses. When combined with ultrasensitive liquid chromatography-MS, nanoPOTS allows identification of ~1500 to ~3000 proteins from ~10 to ~140 cells, respectively. By incorporating the Match Between Runs algorithm of MaxQuant, >3000 proteins are consistently identified from as few as 10 cells. Furthermore, we demonstrate quantification of ~2400 proteins from single human pancreatic islet thin sections from type 1 diabetic and control donors, illustrating the application of nanoPOTS for spatially resolved proteome measurements from clinical tissues. There is a great need of developing highly sensitive mass spectrometry-based proteomics analysis for small cell populations. Here, the authors establish a robotically controlled chip-based nanodroplet processing platform and demonstrate its ability to profile the proteome from 10–100 mammalian cells.

Studies on cognition in multiple system atrophy (MSA) patients are limited. A total of 110 MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales. Approximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and orientation/attention (20%) based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9%) as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2%) showed moderate frontal behavior changes (FBI score 4-15), with incontinence (64.5%) as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931-60.469, P = 0.001) and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002-5.962, P< 0.049) were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631-11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060-7.444, P = 0.038) and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103-13.846, P < 0.0001) were potential determinants of abnormal FAB. Cognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA.