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Abstract Background Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. Methods Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. Result A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation. During the development process, particular attention was given to materials that were tunable, safe, and effective sealant agents. The thermo-responsive properties of poly(N-isopropylacrylamide) (PNIPAM) provides an ideal foundation to develop an optimized solution. Through a combination of model-based and material testing, a hydrogel was developed that balances conformational factors to achieve a customized transition temperature, radiopacity suitable for visualization, mechanical properties suitable for delivery via 3Fr catheter, sufficient cohesion once applied to resist migration under physiological pressures and an improved safety profile. Two applications, embolization of lymphatic leakage and exclusions of the left atrial appendage (LAA), to eliminate LAA dead space to reduce the risk of thromboembolic events, were considered. The material and benchtop results for this product demonstrate the suitability of this new material not only for these applications but also for other potential healthcare applications.

Abstract Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.

Background: We aimed to demonstrate the function of premelanosome protein (PMEL) as a biomarker to predict the effectiveness of mammalian target of rapamycin complex 1 (mTORC1) inhibitor treatment in renal angiomyolipomas (RAMLs) in tuberous sclerosis complex (TSC) patients. Methods: 95 whole blood samples from 49 patients diagnosed with TSC-RAMLs were collected. PMEL, N4BP2, and PCSK1N expression in the plasma samples were tested by quantitative sandwich ELISA. The target tumor volume assessed by maximum cross-sectional area (CSAmax) in CT scans. Correlation analysis was used to determine the relationship between PMEL expression and target tumors, as well as the tumor reduction rate. Results: The tumor size of TSC-RAMLs positivity correlated with PMEL expression (r = 0.30, p = 0.036) and PCSK1N expression (r = 0.23, p = 0.027), but had no significant relationship with N4BP2 (r = 0.06, p = 0.89). The positive correlation between TSC-RAML tumor volume and PMEL expression still existed in TSC patients before (r = 0.30, p = 0.026) and after mTORC1 inhibitor treatment (r = 0.41, p = 0.0017), but the correlation between tumor volume and PCSK1N expression no longer existed. Further analysis found that PMEL expression negatively correlated with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment (r = −0.50, p = 0.0022), both after 3 months (r = −0.47, p = 0.048) and 6 months of treatment (r = −0.52, p = 0.028). Conclusion: PMEL expression positively correlated with the tumor size of TSC-RAMLs, and inversely with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment, which may suggest that PMEL may serve as a predictive biomarker for the efficacy of mTORC1 inhibitor treatment.

Understanding the response of land surface temperature (LST) to urbanization is important for coping with urban warming. However, few studies have discussed the impact of twin-city integration on LST. Here, we explored the relationship between the twin-city integration and LST over the Xi'an-Xianyang Metropolitan Area (XXMA) using the local contour tree algorithm during 2000–2020. Results indicate that: 1) The urban integration of XXMA is obvious, and the spatial scope of XXMA converges toward the Weihe River between the two cities. Besides, its structure tends to be more complex, which develops from 3 levels and 8 centers to 10 levels and 33 centers from 2000 to 2020. 2) The heat islands of XXMA tend to connect and reach the maximum area of 547.43 km2 in 2015, while the LST evolution in two cities is not synchronized. The LST contour tree of Xi'an increased to 6 levels and 26 centers in 2000–2015 and simplified to 5 levels and 17 centers in 2020, while it increased from 1 to 4 levels in Xianyang in 2000–2020. 3) Synergistic effects exist between urban expansion and LST evolution. The correlation coefficient and bivariate Moran's I between nighttime light (NTL) and LST are greater than 0.35, indicating NTL and LST are correlated and have pleasurable spatial consistency. The high–high agglomeration of NTL and LST increases by 132% in area over the 20-year period, showing a trend toward integration. The study results can provide a scientific basis for thermal environment management and urban climate improvement in XXMA.

This paper proposes a multiscale damage identification method for beam-type structures based on node curvature. Firstly, based on the assumption that micro-damage has little effect on stress redistribution and the basic relationship between structural bending moment and curvature, combined with the denoising function of wavelet analysis, the linear matrix equation before and after node curvature damage is solved using the singular value decomposition (SVD) method. Then, the theoretical feasibility of this method is verified with laboratory tests of a simply supported beam. Finally, the damage sensitivity and noise resistance of this method are verified using field measurements of a beam bridge. The results show that the nodal curvature serves as an indicator parameter for damage identification in beam-type structures, enabling the precise localization of damage within these structures. When utilizing a multiscale finite element model for analysis, the nodal curvature enhances the ability to identify both the location and severity of damage within small-scale elements. Furthermore, this method can provide a reference for the damage identification and health monitoring of other types of bridges.

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P

Abstract Diatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana.

With the continuous acceleration of China’s urbanization process, color steel plate, as a new type of building material, has been widely used in all kinds of temporary buildings and has become the spatial carrier of the specific development stage of urbanization. This study focuses on Lanzhou City as a case study to deeply analyze the spatiotemporal distribution and evolution of color steel plate buildings. Utilizing data extracted from Google imagery and GF-2 satellite images of the built-up areas in Lanzhou, spatial statistical and analytical methods such as centroid analysis, compactness index, and patch density are applied. Systematic analysis is conducted across different time periods and spatial scales to examine the evolution of indicators, including quantity, centroid distribution, spatial clustering, and distribution direction. The results show that from 2013 to 2021, the prevalence of color steel buildings in Lanzhou city initially increased and then decreased, and the number peaked in 2017, but there is a significant difference between distinct areas in the urban area. By quantitatively analyzing the spatial and temporal evolution characteristics of color steel plate buildings, this study reveals the important role it plays in promoting the urbanization process and provides a scientific basis for relevant planning decisions.

BackgroundDue to the location of paragangliomas (PGLs) behind the retrohepatic segment of inferior vena cava (IVC), it is difficult to expose and resect the tumor.Case presentationA tumor measuring 50×45×62cm behind the retrohepatic portion of IVC was found in a 51-year-old female with hypertention and diabetes mellitus. Although the test for catecholamines revealed no signs of disease, the enhanced computed tomography (CT) scan, somatostatin receptor imaging and iodine-131-labeled metaiiodo-benzylguanidine (131I-MIBG) imaging revealed that the tumor was PGL. A three-dimensional printing was performed to visualize the tumor. The laparoscpic surgery for the PGL behind the retrohepatic segment of IVC was performed and the tumor was resected completely without causing any tissues injury. The pathologic diagnosis was PGL and the patient was able to recover well.ConclusionsThis case demonstrates that laparoscopic surgery may be helpful in tumor accessibility, and could be used in the appropriate cases to remove PGLs that are located behind the retrohepatic segment of the IVC.

Abstract Photosynthesis is a very important process for the current biosphere which can maintain such a subtle and stable circulatory ecosystem on earth through the transformation of energy and substance. Even though been widely studied in various aspects, the physiological activities, such as intrinsic structural vibration and self‐regulation process to stress of photosynthetic proteins, are still not in‐depth resolved in real‐time. Herein, utilizing silicon nanowire biosensors with ultrasensitive temporal and spatial resolution, real‐time responses of a single photosystem I‐light harvesting complex I (PSI‐LHCI) supercomplex of Pisum sativum to various conditions, including gradient variations in temperature, illumination, and electric field, are recorded. Under different temperatures, there is a bi‐state switch process associated with the intrinsic thermal vibration behavior. When the variations of illumination and the bias voltage are applied, two additional shoulder states, probably derived from the self‐conformational adjustment, are observed. Based on real‐time monitoring of the dynamic processes of the PSI‐LHCI supercomplex under various conditions, it is successively testified to promising nanotechnology for protein profiling and biological functional integration in photosynthesis studies.

In the automated modeling generated by oblique photography, various terrains cannot be physically distinguished individually within the triangulated irregular network (TIN). To utilize the data representing individual features, such as a single building, a process of building monomer construction is required to identify and extract these distinct parts. This approach aids subsequent analyses by focusing on specific entities, mitigating interference from complex scenes. A deep convolutional neural network is constructed, combining U-Net and ResNeXt architectures. The network takes as input both digital orthophoto map (DOM) and oblique photography data, effectively extracting the polygonal footprints of buildings. Extraction accuracy among different algorithms is compared, with results indicating that the ResNeXt-based network achieves the highest intersection over union (IOU) for building segmentation, reaching 0.8255. The proposed “dynamic virtual monomer” technique binds the extracted vector footprints dynamically to the original oblique photography surface through rendering. This enables the selective representation and querying of individual buildings. Empirical evidence demonstrates the effectiveness of this technique in interactive queries and spatial analysis. The high level of automation and excellent accuracy of this method can further advance the application of oblique photography data in 3D urban modeling and geographic information system (GIS) analysis.

The wax deposits of diesel may be formed at low environment temperature during the batch transportation of products pipeline, which will contaminate the subsequent gasoline, resulting in the loss of oil mixing. Therefore, researches on wax deposition of diesel are significant to ensure the economic and efficient operation of products pipelines. Herein, the existing theories on wax deposition were reviewed, and the status of experimental study on wax deposition of diesel was clarified from perspectives of static and dynamic experiments. In addition, the prediction models of wax deposition rate of diesel based on the theories of molecular diffusion and shear dispersion were summarized. Thereby, it is pointed out that strengthening the research on wax deposition mechanism, establishing wax deposition model, and quantitatively characterizing the change rules of quality parameters of the subsequent gasoline with the wax dissolved, are the key direction of research on batch transportation of products pipeline. Besides, by systematically representing the progress of researches on wax deposition of diesel, some reference is provided for the relevant deep researches that may be performed in the future.

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis.Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms.Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism.Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.

Improving far-red light utilization could be an approach to increasing crop production under suboptimal conditions. In land plants, only a small part of far-red light can be used for photosynthesis, which is captured by the antenna proteins LHCAs of photosystem I (PSI) through the chlorophyll (Chl) pair a603 and a609. However, it is unknown how the energy level of Chls a603–a609 is fine-tuned by the local protein environment in vivo. In this study, we investigated how changing the amino acid ligand for Chl a603 in LHCA4, the most red-shifted LHCA in Arabidopsis thaliana, or one amino acid near Chl a609, affected the energy level of the resulting PSI-LHCI complexes in situ and in vitro. Substitutions of the Chl a603 ligand N99 caused a blue shift in fluorescence emission, whereas the E146Q substitution near Chl a609 expanded the emission range to the red. Purified PSI-LHCI complexes with N99 substitutions exhibited the same fluorescence emission maxima as their respective transgenic lines, while the extent of red shift in purified PSI-LHCI with the E146Q substitution was weaker than in the corresponding transgenic lines. We propose that substituting amino acids surrounding red Chls can tune their energy level higher or lower in vivo, while shifting the absorption spectrum more to the red could prove more difficult than shifting to the blue end of the spectrum. Here, we report the first in vivo exploration of changing the local protein environment on the energy level of the red Chls, providing new clues for engineering red/blue-shifted crops.

Background: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear. Objective: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children. Methods: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested. Results: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I–III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differences were found in blood indicators among normal, undernourished and overnourished groups. Conclusion: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP. LAY ABSTRACT Cerebral palsy is the most common physical disability in children in the world. Children with cerebral palsy may have a high risk of having malnutrition as a result of the high energy consumption and/or low energy intake. The former is mainly caused by the abnormal muscular tone, and the latter may emerge from the dysphagia and gastrointestinal problems. As for the optimization of nutritional status is integral to the overall health and clinical management of children with cerebral palsy, the nutritional status stands out for its clinical importance in this group. Children with cerebral palsy are affected by different degrees of motor dysfunction, and may also be faced with eating and drinking problems or limited daily life ability, it is not clear whether nutritional status and function are interrelated. What's more, it is believed that the blood tests may indicate the nutritional status, but it is not well understood. In this project we will look at the nutritional status of children with cerebral palsy in China and investigate the relationship between nutritional status and function and blood indicators. This will then allow clinicians and caregivers to formulate future policies to improve nutritional status for this group of children.

Summary: The light-harvesting complex II of Bryopsis corticulans (B-LHCII), a green alga, differs from that of spinach (S-LHCII) in chlorophyll (Chl) and carotenoid (Car) compositions. We investigated ultrafast excitation dynamics of B-LHCII with visible-to-near infrared time-resolved absorption spectroscopy. Absolute fluorescence quantum yield (ΦFL) of LHCII and spectroelectrochemical (SEC) spectra of Chl a and b were measured to assist the spectral analysis. Red-light excitation at Chl Qy-band, but not Car-band, induced transient features resembling the characteristic SEC spectra of Chl a⋅+ and Chl b⋅−, indicating ultrafast photogeneration of Chl-Chl charge transfer (CT) species; ΦFL and 3Car∗ declined whereas CT species increased upon prolonging excitation wavelength, showing positive correlation of 1Chl∗ deactivation with Chl-Chl CT formation. Moreover, ultrafast Chl b-to-Chl a and Car-to-Chl singlet excitation transfer were illustrated. The red-light induction of Chl-Chl CT species, as also observed for S-LHCII, is considered a general occurrence for LHCIIs in light-harvesting form.

A simple and cost-effective method for the fabrication of a safe, dual-responsive, highly stretchable, self-healing and injectable hydrogel is reported based on a combination of dynamic boronate ester bonds and hydrogen bonding interactions. The mechanical properties of the hydrogel are tunable by adjusting the molar ratios between sugar moieties on the polymer and borax. It was remarkable to note that the 2:1 ratio of sugar and borate ion significantly improves the mechanical strength of the hydrogel. The injectability, self-healing and stretchability properties of the hydrogel were also examined. In addition, the impact of the variation of the pH and the addition of free sugar responsiveness of the hydrogel was studied. High MRC-5 cell viability was noticed by the 3D live/dead assay after 24 h cell culture within the hydrogel scaffold. Hence, the developed hydrogels have desirable features that warrant their applications for drug delivery, scaffolds for cell and tissue engineering.

Abstract Background Vaginal paraganglioma are rare, atypical, solitary tumors which originate from the female genital tract. Sacrococcygeal teratoma are also rare neoplasms which derive from one (or more) primordial germ cell layers. Here we report a unique case of vaginal paraganglioma with sacrococcygeal teratoma. Case presentation A 44-year-old female experienced paroxysmal hypertension, palpitations and dizziness for almost six years. Enhanced CT and MRI highlighted two abnormal soft tissue lesions located in the left vaginal wall and coccyx anteriorly, and Iodine-131 metaiodobenzylguanidine (131I-MIBG) demonstrated abnormal radioactive uptake in perineum area. Endocrine tests showed elevated plasma normetanephrine (NMN) and 24 h urine norepinephrine. There was a well-circumscribed soft tissue lesion of approximately 3.5 cm in the left lateral vaginal wall which could be palpated during bimanual examination, together with a 1.5 cm tumor in the posterior wall of the rectum. We completely resected the two lesions in stages with the support of a senior gynecologist and general surgeons. Postoperative histopathological examinations suggested the vaginal paraganglioma and mature sacrococcygeal teratoma. Targeted sanger sequencing for the 36 mostly common paraganglioma-related genes, with a depth of 1000x, revealed no mutations. Post-operatively, plasma NMN and 24 h urine norepinephrine returned to the normal range and her symptoms completely disappeared. Conclusions We reported an extremely rare case and the successful treatment of functional vaginal paraganglioma coexisting with adult sacrococcygeal teratoma.

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

Transcranial direct current stimulation (tDCS) has shown a promising prospect in improving function and spasticity in school-aged children with cerebral palsy, but little is known in preschool children. The aim of this study was to explore the safety and effects of tDCS on hand function in preschool children (aged 3–6 years) with hemiplegic cerebral palsy (HCP). We designed a crossover, single-blind, sham-controlled study in 30 preschool children with HCP, who were recruited to receive one session of sham and one session of active anodal tDCS (1.5 mA, 20 min) on the primary motor cortex of the affected hemisphere, with a 24-h interval between the two sessions. Questionnaire was completed by each participant and their attendants immediately, 90 min, and 24 h after each session to monitor common adverse events of tDCS, such as skin irritation, skin erythema, burning sensation, headache, dizziness, etc. Box and Block Test, Selective Control of the Upper Extremity Scale, Modified Ashworth Scale, and Melbourne Assessment 2 were conducted at baseline, immediately, and 90 min after each session. No severe adverse event occurred during the study and only a few of them felt transient and slight discomfort. Results also showed that all participants performed better at Box and Block Test of the hemiplegic hand immediately after a single anodal tDCS (P < 0.05) and this improvement lasted at least 90 min and more than 24 h. However, there was no significant improvement in Selective Control of the Upper Extremity Scale of both hands, Box and Block Test of the non-hemiplegic hand, Modified Ashworth Scale, and Melbourne Assessment 2 of the hemiplegic upper limb (P > 0.05). Shortly, this study supported the safety and effects of a single anodal tDCS on improving the manual dexterity of the hemiplegic hand for preschool children with HCP. Further researches with larger samples about the optimal dose and treatment cycle of tDCS for preschool children with HCP are warranted. This study gained the approval of ethics committee of the organization and was registered at chictr.org (ChiCTR2000031141).

Prostate cystadenoma is a rare benign prostatic neoplasm, which grows outside prostate and locates midline between the urinary bladder and rectum. It usually presents as multilocular cysts, thus, named giant multilocular prostate cystadenoma. The definite diagnosis is difficult to be made before surgery, and it depends on histopathology. Here, we report a rarer condition of prostate cystadenoma, which manifests as a giant unilocular cyst with a solid nodule inside. The 55-year-old Chinese male patient presented with dysuria and constipation. MRI revealed a 10.5 × 8.2 cm mono-cystic lesion displacing the rectum to the posterior, prostate, and bladder to the anterior, with a 2.8 × 2.1 cm solid nodule at the anterior wall. 18F-FDG PET/CT demonstrated an elevated SUVmax (3.5) of the solid nodule. Laparoscopic pelvic mass resection was performed and prostate cystadenoma was diagnosed. In conclusion, when a mass of single locular cyst sits in the male pelvis, the diagnosis of prostate cystadenoma could not be excluded.

BackgroundEverolimus has been approved in China for adult patients with TSC-AML (tuberous sclerosis associated renal angiomyolipomas) not requiring immediate surgery and has been previously shown to be an effective treatment option for TSC-AML in the Chinese populationMethodsThis is an open label, single arm, multi-center Phase IV post-approval commitment study to further assess the safety and efficacy of everolimus in patients with TSC-AML who do not require immediate surgical intervention. The primary outcome was to evaluate the safety of everolimus while the secondary outcome was to evaluate AML response.ResultsTreatment with everolimus was associated with a clinically meaningful best overall AML response rate of 70% (95% CI: 53.5, 83.4). Of the 38 evaluable patients, 37 (97%) patients experienced a reduction in the sum of volumes of target angiomyolipoma lesions relative to baseline. At Week 12 (n=38), the median percentage change in sum of target AML volume was −56.60%, which further changed by -59.96% at Week 24 (n=38), and by −64.41% at Week 48 (n=22). Throughout the study, renal function remained relatively stable. Patients with TSC associated lymphangiomyomatosis (LAM) (N=13) demonstrated a lower than expected rate of decline in pulmonary function tests (PFTs). Everolimus was generally well tolerated with no significant safety findings in Chinese patients. Most of the adverse events were of grade 1-2, and manageable with appropriate dose adjustments and supportive therapies. There were no treatment discontinuation due to AE and no treatment death was reported.ConclusionsBased on the efficacy and safety data presented in this study, the overall clinical benefit/risk assessment further supports the use of everolimus as a viable treatment option for Chinese patients with TSC-AML.

Abstract Plants harvest light energy utilized for photosynthesis by light-harvesting complex I and II (LHCI and LHCII) surrounding photosystem I and II (PSI and PSII), respectively. During the evolution of green plants, moss is at an evolutionarily intermediate position from aquatic photosynthetic organisms to land plants, being the first photosynthetic organisms that landed. Here, we report the structure of the PSI–LHCI supercomplex from the moss Physcomitrella patens (Pp) at 3.23 Å resolution solved by cryo-electron microscopy. Our structure revealed that four Lhca subunits are associated with the PSI core in an order of Lhca1–Lhca5–Lhca2–Lhca3. This number is much decreased from 8 to 10, the number of subunits in most green algal PSI–LHCI, but the same as those of land plants. Although Pp PSI–LHCI has a similar structure as PSI–LHCI of land plants, it has Lhca5, instead of Lhca4, in the second position of Lhca, and several differences were found in the arrangement of chlorophylls among green algal, moss, and land plant PSI–LHCI. One chlorophyll, PsaF–Chl 305, which is found in the moss PSI–LHCI, is located at the gap region between the two middle Lhca subunits and the PSI core, and therefore may make the excitation energy transfer from LHCI to the core more efficient than that of land plants. On the other hand, energy-transfer paths at the two side Lhca subunits are relatively conserved. These results provide a structural basis for unravelling the mechanisms of light-energy harvesting and transfer in the moss PSI–LHCI, as well as important clues on the changes of PSI–LHCI after landing.

Photosystems (PS) I and II undergo state transitions to optimize photosynthesis and photoprotection. Here the authors report a cryo-electron microscopy structure of the state 2 PSI-LHCI-LHCII supercomplex from C. reinhardtii revealing subunit organization and possible pathways of energy transfer.

BackgroundTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with systemic organ involvement. So far, only a few TSC families in China have been reported. Therefore, more data on the clinical and genetic features of TSC families are required.Materials and MethodsWe retrospectively analyzed 12 TSC family probands and their family members. Next-generation sequencing (NGS) has been applied to confirm the type of TSC mutation along with a detailed physical examination.ResultsIn this study, twenty-seven patients in 12 TSC families were reported, including 12 male and 15 female patients, aged 8–67 years. Skin lesions were detected among all patients with TSC, including 25 cases of facial angiofibromas, 18 cases of hypomelanotic macules, 15 cases of ungual fibromas, and 13 cases of shagreen patch. Other clinical features were also revealed: 14 cases of renal angiomyolipoma, 6 cases of subependymal nodules (SENs), and 3 cases of lymphangioleiomyomatosis. All twenty-seven patients with TSC were tested by NGS. Totally, TSC2 mutations were reported in 19 cases (7 frameshift mutations, 10 nonsense mutations, and 2 missense mutations), TSC1 mutations were reported in 4 cases (4 nonsense mutations), and 4 cases were genetically negative. The novel causal mutations (TSC2: c.208dup, c.1874C > G, c.1852del) identified in three families were first reported in TSC.ConclusionOur findings expand the mutation spectrum of patients with TSC in China. The clinical characteristics can vary among patients with TSC with the same pathogenic mutation. The genetic results and summary of clinical features of 12 TSC families contribute to a more accurate diagnosis and further genetic counseling.

Abstract We sought to explore the relationship between renal lesion features and genetic mutations in tuberous sclerosis complex (TSC) patients. TSC patients with renal lesions were subjected to TSC1/2 gene next-generation sequencing (NGS). TSC1/2 mutation types and imaging examinations were screened for combined analysis of genetic and clinical features. Seventy-three probands among TSC patients with renal lesions were included. Twenty affected relatives were also included. In total, 93 patients were included. Eighty patients (86.0%) had bilateral renal angiomyolipomas (AMLs), and one had epithelioid AML. Two patients had polycystic kidney disease, one had renal cell carcinoma, and one had Wilms tumor. Among the 73 probands, four had TSC1 mutations, 53 had TSC2 mutations, and 16 had no mutations identified (NMI). There was no statistically significant difference between TSC1 mutation, TSC2 mutation and NMI group (P= 0.309), or between familial and sporadic groups (P= 0.775) when considering AML size. There was no statistically significant difference between pathogenic/likely pathogenic and benign/likely benign/NMI groups (P= 0.363) or among patients with different mutation types of TSC2 (P= 0.906). The relationship between the conditions of TSC gene mutations and the severity of renal lesions still needs more analysis. Patients with NMI, particularly those with familial disease, need more attention because the pathogenesis remains unknown.

Diatoms are marine algae with an important role in global photosynthetic carbon fixation. Here, the authors present the 2.38 Å cryo-EM structure of photosystem I (PSI) in complex with its 24 fucoxanthin chlorophyll a/c-binding (FCPI) antenna proteins from the diatom Chaetoceros gracilis, which provides mechanistic insights into light-energy harvesting, transfer and quenching of the PSI-FCPI supercomplex.

Ectopic Cushing’s syndrome due to ectopic ACTH&CRH-secreting by pheochromocytoma is extremely rare and can be fatal if not properly diagnosed. It remains unclear whether a unique cell type is responsible for multiple hormones secreting. In this work, we performed single-cell RNA sequencing to three different anatomic tumor tissues and one peritumoral tissue based on a rare case with ectopic ACTH&CRH-secreting pheochromocytoma. And in addition to that, three adrenal tumor specimens from common pheochromocytoma and adrenocortical adenomas were also involved in the comparison of tumor cellular heterogeneity. A total of 16 cell types in the tumor microenvironment were identified by unbiased cell clustering of single-cell transcriptomic profiles from all specimens. Notably, we identified a novel multi-functionally chromaffin-like cell type with high expression of both POMC (the precursor of ACTH) and CRH, called ACTH+&CRH + pheochromocyte. We hypothesized that the molecular mechanism of the rare case harbor Cushing’s syndrome is due to the identified novel tumor cell type, that is, the secretion of ACTH had a direct effect on the adrenal gland to produce cortisol, while the secretion of CRH can indirectly stimulate the secretion of ACTH from the anterior pituitary. Besides, a new potential marker (GAL) co-expressed with ACTH and CRH might be involved in the regulation of ACTH secretion. The immunohistochemistry results confirmed its multi-functionally chromaffin-like properties with positive staining for CRH, POMC, ACTH, GAL, TH, and CgA. Our findings also proved to some extent the heterogeneity of endothelial and immune microenvironment in different adrenal tumor subtypes.

Fucoxanthin is an oxygenated carotenoid component that has been reported to play important roles in anti-oxidation, anti-obesity and anti-cancer in the human body. Fucoxanthin-chlorophyll protein (FCP) complexes participate in light harvesting and photoprotection in diatom. In order to better understand the change of fucoxanthin content and its role in photoprotection, the growth, fucoxanthin biosynthesis and photosynthetic phenotypes were studied in the diatom Phaeodactylum tricornutum under the treatment of exogenous arachidonic acid (AA). Our results demonstrated that even low concentration of AA at 0.1 mg/L strongly induced fucoxanthin accumulation in algal cells to a maximum of 1.1 mg/g dry weight (DW), which was 36.6% higher than that in the untreated ones. By principal component analysis (PCA), we also identified a close correlation between fucoxanthin accumulation and the expression of genes involved in fucoxanthin biosynthesis, especially phytoene synthase (PSY), suggesting that AA change the metabolism of fucoxanthin by inducing carotenoid metabolic enzymes at the transcriptional level. Furthermore, we found that the exogenous application of AA affected non-photochemical quenching (NPQ) and photoinhibition, which resulted from the changed diadinoxanthin (DD) and diatoxanthin (DT) cycle, and thus played an important role in photoprotection.

Pure WO3 sensors and Mn3O4/WO3 composite sensors with different Mn concentrations (1 atom %, 3 atom % and 5 atom %) were successfully prepared through a facile hydrothermal method. As gas sensing materials, their sensing performance at different temperatures was systematically investigated for gas detection. The devices displayed different sensing responses toward different gases at specific temperatures. The gas sensing performance of Mn3O4/WO3 composites (especially at 3 atom % Mn) were far improved compared to sensors based on pure WO3, where the improvement is related to the heterojunction formed between the two metal oxides. The sensor based on the Mn3O4/WO3 composite with 3 atom % Mn showed a high selective response to hydrogen sulfide (H2S), ammonia (NH3) and carbon monoxide (CO) at working temperatures of 90 °C, 150 °C and 210 °C, respectively. The demonstrated superior selectivity opens the door for potential applications in gas recognition and detection.

Mechanical pigging is a major wax removal technique in crude oil pipeline transportation. To lower the risk of pig stalling accidents in pigging, a superparamagnetic nanoparticle (SPM-NP) pigging system that consists of an electromagnetic pig and nanopaint is designed to soften the wax deposit and reduce the wax resistive force. During pigging, the induction coil on the pig generates an alternating magnetic field, which induces heat production of the nanopaint on the pipe wall. The COMSOL software is used to simulate the temperature distribution of the wax layer. Yield stress measurements reveal that the wax layer yield stress is nearly linearly correlated to temperature. Compared with a regular pig, the SPM-NP pigging system reduces the wax resistive force by up to 20~40%, with an acceptable electrical current intensity of about 20 A in the given cases. Multiple factors affecting the wax layer temperature were analyzed. SPM-NP heating could be a promising technique for wax remediation and hydrate prevention.

Multimodal cocktail periarticular injections comprising corticosteroids are the most suggested therapy for postoperative discomfort and swelling following total knee arthroplasty (TKA). Nevertheless, previous findings cannot be applied to instances of unilateral total knee arthroplasty on bilateral knees. This randomized, prospective, double-blind, controlled clinical study examines the efficacy as well as safety of periarticular multimodal cocktail injection along or sans corticosteroids in certain situations. The 60 patients (120 knees) that experienced concurrent bilateral total knee arthroplasty were provided periarticular injections along additional betamethasone (7 mg) in the randomized knee, as well as the other knee, where corticosteroid was not administered. Key results were “pain scores at rest as well as in action” on a visual analogue scale of 11 pt. Other results included motion range, swelling of the thigh, Hospital for Special Surgery score (HSS score), and adverse effects were measured between the two sides. No statistically promising variations were found in the visual analogue scale ranking, motion range, girth of the thigh, and HSS score, as well as complications between the two sides. The impact on treatment outcomes was maintained between the knees on postoperative day 3 or at 3 months of follow-up. Multimodal periarticular injection without corticosteroid will alleviate postoperative swelling and pain. More studies are needed for the use of betamethasone as a corticosteroid in periarticular multimodal cocktail injections. This Chinese Clinical Trial Registry is registered with ChiCTR-OPC-17013503, dated 2017-11-23, available from http://www.chictr.org.cn/showproj.aspxproj=23146.

Abstract Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the development of numerous benign tumors. Renal angiomyolipoma (RAML) occur in up to 80% of TSC patients, which is a leading cause of TSC-related death in adult patients. The aim of the study was to evaluate the efficacy and safety profiles of everolimus in Chinese patients of TSC associated with RAML(TSC-RAML). Methods In this 2-years, nonrandomized, open-label trial, 18 patients of TSC-RAML, with at least one RAML 3 cm or larger in its longest diameter, were enrolled to assess the efficacy and safety of everolimus therapy in Chinese patients. Everolimus was administered for the first 12 months only. The primary endpoint was a reduction of 50% or more relative in RAML volume to the baseline in the absence of new RAML ≥1 cm and no RAML-related bleeding of grade ≥ 2. The secondary endpoints included: safety, lung function and skin lesions response rate. Serial computed tomography of RAML, magnetic resonance imaging of brain lesions and pulmonary-function tests were performed. Adverse events were investigated using CTCAE v4.0. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software. Results The proportion of patients who achieved ≥50% reduction from baseline in the sum of volumes of target lesions increased from 52.94% at 3 months, to 58.82% and 66.67% at months 6 and 12, respectively. During the period of everolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 s (FEV1) increased by 276 ± 78 ml (P

Accumulating evidence has shown enhanced sensorimotor control of vocal production as a consequence of extensive singing experience. The neural basis of this ability, however, is poorly understood. Given that the insula mediates motor aspects of vocal production, the present study investigated structural plasticity in insula induced by singing experience and its link to auditory feedback control of vocal production. Voxel-based morphometry (VBM) was used to examine the differences in gray matter (GM) volume in the insula of 21 singers and 21 non-singers. An auditory feedback perturbation paradigm was used to examine the differences in auditory-motor control of vocal production between singers and non-singers. Both groups vocalized sustained vowels while hearing their voice unexpectedly pitch-shifted −50 or −200 cents (200 ms duration). VBM analyses showed that singers exhibited significantly lower GM volumes in the bilateral insula than non-singers. When exposed to pitch perturbations in voice auditory feedback, singers involuntarily compensated for pitch perturbations in voice auditory feedback to a significantly lesser degree than non-singers. Moreover, across the two sizes of pitch perturbations, the magnitudes of vocal compensations were positively correlated with the total regional GM volumes in the bilateral insula. These results indicate that extensive singing training leads to decreased GM volumes in insula and suggest that morphometric plasticity in insula contributes to the enhanced sensorimotor control of vocal production observed in singers.

This paper theoretically analyzed the deformation law of the underlying tunnel caused by dewatering and excavation of deep foundation pit in the phreatic aquifer area, which is based on the Mindlin solution and the double-sided elastic foundation beam theory, and used the finite difference method and the fluid-solid coupling principle to conduct three-dimensional numerical simulation of dewatering and excavation of deep foundation pit with fluid-solid coupling by using FLAC3D5.00. This research shows that the layered and segmented excavation method from the middle to the end by dewatering the skip layer has a better effect on optimizing the deformation of the underlying tunnel through the simulation of three excavation methods and two dewatering schemes crossing each other, which is about 2.5% less than the layer-by-layer dewatering scheme. In addition, the deformation law of the simulated value is the same as the theoretical value, and the simulated value is slightly larger than the theoretical value. Underlying tunnel only just exists vertical deformation at the direct center of the foundation pit, and the maximum deformation is about 3.054 mm under the dewatering well of the jumping layer and W3. With the dewatering of jumping layer and the third excavation mode (W3), underlying tunnel only just exists lateral displacement at the position where is the retaining structure, and the maximum displacement is 1.606 mm.

The spatial distribution of fire stations is an important component of both urban development and urban safety. For expanding mega-cities, land-use and building function are subject to frequent changes, hence a complete picture of risk profiles is likely to be lacking. Challenges for prevention can be overwhelming for city managers and emergency responders. In this context, we use points of interest (POI) data and multi-time traffic situation (MTS) data to investigate the actual coverage of fire stations in central Beijing under different traffic situations. A method for identifying fire risks of mega cities and optimizing the spatial distribution of fire stations was proposed. First, fire risks associated with distinctive building and land-use functions and their spatial distribution were evaluated using POI data and kernel density analysis. Furthermore, based on the MTS data, a multi-scenario road network was constructed. The “location-allocation” (L-A) model and network analysis were used to map the spatial coverage of the fire stations in the study area, optimized by combining different targets (e.g., coverage of high fire risk areas, important fire risk types). Results show that the top 10% of Beijing’s fire risk areas are concentrated in “Sanlitun-Guomao”, “Ditan-Nanluogu-Wangfujing”, and “Shuangjing-Panjiayuan”, as well as at Beijing Railway Station. Under a quarterly average traffic situation, existing fire stations within the study area exhibit good overall POI coverage (96.51%) within a five-minute response time. However, the coverage in the northwest and southwest, etc. (e.g., Shijicheng and Minzhuang) remain insufficient. On weekdays and weekends, the coverage of fire stations in the morning and evening rush hours fluctuates. Considering the factors of high fire risk areas, major fire risk types, etc. the results of optimization show that 15 additional fire stations are needed to provide sufficient coverage. The methods and results of this research have positive significance for future urban safety planning of mega-cities.

Self-assemblies of polymers to form polymersomes in solution can be used as carriers for drug delivery, but it is challenging to control polymer crystallization to improve their mechanical stability. Here, Wang et al.show the formation of nanosized crystalsomes composed of polymer lamellar single crystals.

Hydrogels are three-dimensional cross-linked polymer networks which can absorb and retain large amount of water. As representative soft materials with tunable chemical, physical and biological properties, hydrogels with different functions have been developed and utilized in a broad range of applications, from tissue engineering to soft robotics. However, conventional hydrogels usually suffer from weak mechanical properties and they are easily deformed or damaged when they are subjected to mechanical forces. The accumulation of the damage may lead to the permanent structural change and the loss of the functional properties of the hydrogels. Therefore, it is important to develop mechanically robust hydrogels with autonomous self-healing property in order to extend their lifespan for various applications. In this mini review, we focus on the discussion about the appropriate molecular design of the hydrogel network for achieving self-healing and excellent mechanical properties, respectively as well as the corresponding self-healing and toughening mechanisms. We conclude with perspectives on the remaining challenges in the field as well as the recommendations for future development.

Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs, a series of essential oil-based β-methoxyacrylate derivatives have been designed and synthesized. The target compounds have been screened for their potential fungicidal activity against eleven species of plant pathogen fungi, including Alternaria alternata, Phomopsis adianticola, Pestalotiopsis theae, Sclerotinia sclerotiorum, etc. Compared with intermediates I, the parent essential oils and azoxystrobin, almost all of essential oil-based β-methoxyacrylate derivatives exhibited significantly better fungicidal activity. Further investigation revealed that some compounds showed remarkable inhibitory activities against Pestalotiopsis theae, Phomopsis adianticola, Sclerotinia sclerotiorum and Magnapothe grisea at different concentrations in contrast to the commercial product azoxystrobin. Compound II-8 exhibited particularly significant fungicidal activity.