Disorders of compulsivity: Deficits in arbitrating learning strategies.

While previous research has shown that compulsivity is related to an imbalance between goal-directed and habitual learning systems, very little is known about whether this effect is due to the impairment of a single system or the impairment of the arbitration mechanism that determines which system controls behaviour at any given moment; the current study aims to address this disagreement. Nineteen alcohol use disorder, 30 obsessive-compulsive disorder (OCD) and 20 major depressive disorder patients and corresponding sex- and age-matched controls performed two-choice, three-stage Markov decision-making paradigm. Model-based and mode-free reinforcement learning models were used to independently fitted their behavioural data. Alcohol use disorder and OCD patients showed less model-based strategy choice than healthy controls in task conditions where the model-based strategy was optimal. Only OCD patients showed higher behavioural control system switching in task conditions where model-free use was optimal. Major depressive disorder patients did not differ from the matched control in both. These findings suggest that dysfunction in arbitration control between dual systems may be the basis for diverse disorders involving compulsivity.

Soft-Mode-Phonon-Mediated Unconventional Superconductivity in Monolayer 1T

Recent experiments have tuned the monolayer 1T^{'}-WTe_{2} to be superconducting by electrostatic gating. Here, we theoretically study the phonon-mediated superconductivity in monolayer 1T^{'}-WTe_{2} via charge doping. We reveal that the emergence of soft-mode phonons with specific momentum is crucial to give rise to the superconductivity in the electron-doping regime, whereas no such soft-mode phonons and no superconductivity emerge in the hole-doping regime. We also find a superconducting dome, which can be attributed to the change of Fermi surface nesting conditions with electron doping. By taking into account the experimentally established strong anisotropy of temperature-dependent upper critical field H_{c2} between the in-plane and out-of-plane directions, we show that the superconducting state probably has the unconventional equal-spin-triplet pairing in the A_{u} channel of the C_{2h} point group. Our studies provide a promising understanding to the doping dependent superconductivity and strong anisotropy of H_{c2} in monolayer 1T^{'}-WTe_{2}, and can be extended to understand the superconductivity in other gated transition metal dichalcogenides.

Polylysine modified conjugated polymer nanoparticles loaded with the singlet oxygen probe 1,3-diphenylisobenzofuran and the photosensitizer indocyanine green for use in fluorometric sensing and in photodynamic therapy.

Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (1O2 probe). The nanoparticle core consists of the energy donating host poly(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene) (PFP). The polymer is doped with the energy acceptor DPBF. Ratiometric fluorometric detection of singlet oxygen is accomplished by measurement of fluorescence at wavelengths of 415 and 458 nm. In addition, the shell of the positively charged polymeric nanoparticles was modified, via electrostatic interaction, with negatively charged PDT drugs ICG. The integrated nanoparticles of type ICG-DPBF-PFP display effective photodynamic performance under 808-nm laser irradiation. The 1O2 sensing behaviors of samples are evaluated based on the ratiometric fluorescent responses produced by DPBF and PFP. 1O2 can be fluorimetically sensed with a detection limit of 28 µM. The multifunctional nanoprobes exhibit effortless cellular uptake, superior photodynamic activity and a rapid ratiometric response to 1O2. Graphical abstractSchematic of a dual-functional nanoplatform for photodynamic therapy (PDT) and singlet oxygen (1O2) feedback. It offers a new strategy for self-monitoring photodynamic ablation. FRET: fluorescence resonance energy transfer. Indocyanine green is attached in the shell of nanoparticles, and 1,3-diphenylisobenzofuran is doped into the energy donating host conjugated polymer.

Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells.

There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.

Processing of cellulose synthase (AcsAB) from Gluconacetobacter hansenii 23769.

The cellulose synthase protein (AcsAB) is encoded by a single gene in Gluconacetobacter hansenii ATCC 23769. We have examined the processing pattern of this enzyme and the localization of the cleavage products by heterologously expressing the truncated portions of the AcsAB protein and using specific antibodies generated against these regions. We found that the AcsAB protein is processed into three polypeptide subunits of molecular masses 46kDa, 34kDa and 95kDa. The 46kDa polypeptide (AcsA(cat)) harbors the conserved glycosyltransferase domain and hence contains the catalytic subunit of the enzyme. This polypeptide is localized in the cytoplasmic membrane. The 34kDa polypeptide (AcsA(reg)) is the regulatory subunit with the cyclic diGMP-binding PilZ domain. This polypeptide is largely cytoplasmic. The 95kDa subunit (AcsB) is of unknown function and contains a predicted signal peptide at its N-terminus. This subunit is localized in the outer membrane. In addition to this, we have also localized the AcsC protein in the outer membrane, confirming its predicted localization based on the OM-signal sequence at its N-terminus.

Application of three-dimensional imaging to the intestinal crypt organoids and biopsied intestinal tissues.

Two-dimensional (2D) histopathology is the standard analytical method for intestinal biopsied tissues; however, the role of 3-dimensional (3D) imaging system in the analysis of the intestinal tissues is unclear. The 3D structure of the crypt organoids from the intestinal stem cell culture and intestinal tissues from the donors and recipients after intestinal transplantation was observed using a 3D imaging system and compared with 2D histopathology and immunohistochemistry. The crypt organoids and intestinal tissues showed well-defined 3D structures. The 3D images of the intestinal tissues with acute rejection revealed absence of villi and few crypts, which were consistent with the histopathological features. In the intestinal transplant for megacystis microcolon intestinal hypoperistalsis syndrome, the donor's intestinal tissues had well-developed nerve networks and interstitial cells of Cajal (ICCs) in the muscle layer, while the recipient's intestinal tissues had distorted nerve network and the ICCs were few and sparsely distributed, relative to those of the donor. The 3D images showed a clear spatial relationship between the microstructures of the small bowel and the features of graft rejection. In conclusion, integration of the 3D imaging and 2D histopathology provided a global view of the intestinal tissues from the transplant patients.

The Health Insurance Fund Participates in Controlling the Epidemic: Insights from German Experience in Dealing with the COVID-19 Pandemic.

To reveal the importance of the participation of the health insurance fund in the prevention and control of serious infectious diseases, this research retrospectively analyzed the case of the German statutory health insurance fund in response to the COVID-19 epidemic. Based on Germany's practical experience, this research offers a strategy idea for other countries with a social health insurance system, aiming to ensure that the health care system does not collapse rapidly due to medical resource shortage in the event of a pandemic. Firstly, this research conducted a documentary analysis to systematically collate the temporary and additional coverage measures provided by the health insurance fund from January to the end of July 2020, which sheds light on the pivotal role of these funds in epidemic prevention and control. Secondly, this research used comparative analysis to examine the time sequence of implementing these different types of coverage measures in the progression of the epidemic to illustrate how the health insurance fund adjusted its response measures. The health insurance fund was actively involved in the development of core strategies for combating the epidemic when it broke out, by taking part in joint multisectoral consultations. By using payment instruments flexibly, the fund led the implementation of epidemic prevention and control measures, as it could allocate health resources quickly and efficiently in emergencies. Furthermore, the health insurance fund played a critical role in transmitting information on the epidemic and guiding the insured to take appropriate protective measures. By fulfilling its role in health promotion, particularly in the area of health education, the fund provided important complementary and synergistic contributions to the prevention and control of the spread of infectious diseases. In summary, this research provides a new model for other countries for mobilizing a multi-sectoral response to infectious disease prevention and control, and emphasises the key role of the health insurance fund in responding to major public health crises.

GPs in UK: From Health Gatekeepers in Primary Care to Health Agents in Primary Health Care.

After 75 years of reformed practice, general practitioners (GPs) in the UK have transformed from health gatekeepers who simply provide medical decision-making such as diagnostic and treatment services and referral services, to health agents who proactively provide more relevant health services such as immunizations, health monitoring and health management, etc. In order to discuss this transformation of the role of the general practitioner and the conditions for the evolution of the role, this study chose the documentary analysis method to provide a comprehensive overview of the legal and normative documents related to the general practitioner. Furthermore, this study uses a comparative analysis method to conclude the definition and role characteristics of GPs as health agents. This study summarises the general pattern of evolution of GPs into health agents. The transformation into a health agent relies on the interpersonal trust and rigorous institutional of society on the general practitioner system. The expansion of GPs' clientele and range of services, together with the motivation to proactively provide services, have combined to push for a "qualitative change" in the GP's role as health agent. The transformation of the role of the general practitioner to a health agent is a historical necessity. It responds to the evolution of society's understanding of health and the need for higher levels of health. Therefore, recognizing the role of GPs as health agents is important for optimizing the use of health care resources and improving the health of society by taking advantage of this role.

3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing.

Morphological changes of interstitial cells of Cajal (ICC) have been proposed to characterize motility disorders. However, a global view of the network orientations of ICC subgroups has not been established to illustrate their three-dimensional (3-D) architectures in the human colon. In this research, we integrate c-kit immunostaining, 3-D microscopy with optical clearing, and image rendering to present the location-dependent network orientations with high definition. Full-depth colonic tissues were obtained from colectomies performed for nonobstructing carcinoma. Specimens of colon wall were prepared away from the tumor site. C-kit and nuclear fluorescent staining were used to identify the ICC processes and cell body. Optical clearing was used to generate transparent colon specimens, which led to panoramic visualization of the fluorescence-labeled ICC networks at the myenteric plexus (ICC-MY), longitudinal (ICC-LM) and circular (ICC-CM) muscles, and submucosal boundary (ICC-SM) up to 300 µm in depth via confocal microscopy with subcellular level resolution. We observed four distinct network patterns: 1) periganglionic ICC-MY that connect with ICC-LM and ICC-CM, 2) plexuses of ICC-LM within the longitudinal muscle and extending toward the serosa, 3) repetitive and organized ICC-CM layers running parallel to the circular muscle axis and extending toward the submucosa, and 4) a condensed ICC-SM layer lining the submucosal border. Among the four patterns, the orderly aligned ICC-CM layers provide an appropriate target for quantitation. Our results demonstrate the location-dependent network orientations of ICC subgroups and suggest a practical approach for in-depth imaging and quantitative analysis of ICC in the human colon specimen.

Responses of the macrobenthic community to the Dalian Bay oil spill based on co-occurrence patterns and interaction networks.

On July 16, 2010, a pipeline explosion spilled 1500 tons of crude oil into the Port of Dalian, China. To identify taxa responses to the spill, we exploited seven years of monitoring data to examine the co-occurrence of taxon pairs and the variation of the macrobenthic community. Non-parametric correlation analysis was used to construct interaction networks of relationships between oil spill contaminants and macrobenthic taxa. We observed that the impacted macrobenthic community not restored before 2016. The tolerance/sensitivity of taxa was inconsistent with the studies of oil impacts in other locations. We suggest revision of the ecological group classification of Sabellidae, Lumbrineridae, Terebellidae, Sternaspidae, and Spionidae. The variation in the frequency of coexistence indicates the potential impact of oil spill pollution on resource occupation. The interaction network involving macrobenthic families and stressors associated with the oil spill highlights how different macrobenthic families respond to different combinations of stressors.

Chlorin e6-1,3-diphenylisobenzofuran polymer hybrid nanoparticles for singlet oxygen-detection photodynamic abaltion.

A dual-functional nanosysterm is developed by means of Chlorin e6 (Ce6) as photosensitizer and 1,3-Diphenylisobenzofuran (DPBF) as fluorescent singlet oxygen (1O2) probe. Under 660 nm laser irradiation, Ce6 exhibites efficient 1O2 generation, and subsequently the production of 1O2 is assessed by the ratiometric fluorescence of PFO and DPBF under one-photon and two-photon excitation mode. The nanoparticles with excellent biocompatibility can be internalized into Hela cells and applied for tumor treatment. For intracellular PDT, the nanoparticles perform a high phototoxicity, while the PDT proccess can be evaluated in time by monitoring fluorescence signals of DPBF. This theranostic nanosysterm provides a facile strategy to fabricate 1O2-detection PDT, which can realize accurate and efficient photodynamic therapy based on singlet oxygen detection.

Chemical control of overwintering green algae to mitigate green tide in the Yellow Sea.

It has been 14 years since the world's largest Ulva bloom appeared in the Yellow Sea, China in 2007. Although it is clear that the Ulva bloom originates from the culture system of Porphyra yezoensis (Nori) in the southern Yellow Sea, how to control it is still little understood. Since overwintering banks played a crucial role in the development of spring population of green algae on the cultivation ropes, here, a promising method was presented to prevent the development of Ulva bloom by the inactivation of the overwintering banks of green algae on the P. yezoensis cultivation ropes during February and early March. Chlorine dioxide, an environment-friendly disinfectant was used as algaecide with dosage of no lower than 40 mg/L at the contact time of 1 min. The overwintering green algae gradually disappeared within two weeks after the treatment. Furthermore, the growth of spring population of green algae on the cultivation ropes was effectively inhibited for at least eight weeks, which contribute to prevent the formation of floating populations during cultivation facilities collection. It was expected that the present method, if to be applied in the P. yezoensis cultivation areas in southern Yellow Sea, may mitigate the magnitude of the Ulva blooms in the Yellow Sea at a lower cost.

Deodorizing for fiber and fabric: Adsorption, catalysis, source control and masking.

Textile with deodorizing properties not only keeps the clothing smell fresh, but also is beneficial toward improving the level of indoor air quality, especially when the fibrous materials are used for buildings and furniture. This review summarizes and discusses the recent progress in developing smart textile with deodorizing property. In particular, the key deodorizing methods including enhanced adsorption, catalytic decomposition, source control and masking are brought to light. The theoretical concepts, mechanisms and the latest fabrication methods along with the deodorizing efficiency are discussed. Moreover, the current limitations of these methods are underlined and some recommendations for future research strategies in terms of deodorizing performance, textile engineering, fiber types and treatment impact on fiber mechanical properties are proposed. This review provides the latest state-of-the-art achievements in the field of deodorizing methods of textile, which will be a valuable platform for researchers and decision makers to design and develop novel functional textile products.

Facile synthesis of polypyrrole-rhodamine B nanoparticles for self-monitored photothermal therapy of cancer cells.

Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.

Long-term results of modified ligament reconstruction and tendon interposition for thumb basal joint arthritis.

BACKGROUND: Thumb basal joint arthritis is a common, disabling condition of the hand. Ligament reconstruction and tendon interposition (LRTI) is one of the more common surgical solutions. We performed a retrospective study to evaluate long-term radiological and clinical outcomes of modified LRTI procedures in treating thumb basal joint arthritis. METHODS: A total of 91 hands (84 patients) with full chart records were enrolled in this study. The average age was 65.4 years, and the mean follow-up was 11.7 years (range, 1-21.6 years). We evaluated pain, joint stability, power-grip and key pinch strength, and thumb radial abduction angle as the functional outcomes, and measured the height of the trapezial space as the radiographic result. RESULTS: There were 66 and 23 hands with excellent and good results, respectively. The diminution of the trapezial space was 4.2 mm in the stage III group and 5.2 mm in the stage IV group. Power-grip and key pinch strength, and thumb radial abduction angle were better in those with stage III than in those with stage IV arthritis. Sixty-eight hands were followed up >5 years, and of them, 66 showed excellent or good results. CONCLUSION: With good and durable surgical outcomes, the modified LRTI procedure could be a good treatment for thumb basal joint arthritis.

Two-photon oxygen nanosensors based on a conjugated fluorescent polymer doped with platinum porphyrins.

Ratiometric fluorescent nanoparticles (NPs) under two-photon excitation are successfully developed for sensing dissolved oxygen. The NPs comprise the oxygen probe Pt(II)-porphyrins (PtTFPP) and fluorescent organic semiconducting polymer (PFO). PFO polymer acts as both a two-photon antenna and a reference dye, while PtTFPP absorbs the photonic energy transferred by the PFO under two-photon excitation at 740 nm to sense oxygen. The red fluorescence of PtTFPP is sensitive to oxygen with a quenching response of 88% from nitrogen saturation to oxygen saturation, and PFO gives oxygen-insensitive referenced blue fluorescence. The fluorescence quenching of the NPs against oxygen at two-photon excitation follows a linear Stern-Volmer behavior. The nanosensors exhibit low cytotoxic effects as well as effortless cellular uptake. When incorporated into cells, the ratio of the signals increases up to about 500% from oxygen-saturated to oxygen-free environment.

Recurrence rate of the Paine retinaculotome carpal tunnel release in diabetic and non-diabetic patients at long-term follow-up.

BACKGROUND: Carpal tunnel release (CTR) is considered effective in treating carpal tunnel syndrome (CTS), and diabetes is considered to complicate the outcome and recovery. However, the difference in recurrence rate between diabetic and non-diabetic patients after mini-open CTR in the long-term has not yet determined. METHODS: This study enrolled 1251 wrists (1091 patients), with 841 (67%) females and 480 (33%) males at a mean age of 58.5 years at operation. Patients were followed for a mean duration of 10.5 years. We retrospectively compared the recurrence rates of the Paine retinaculotome for mini-open CTR at wrist in diabetic and non-diabetic patients. RESULTS: In our study, a total of 161 wrists (13%) were in the diabetic patients and 1090 wrists (87%) were in the non-diabetic patients. Two wrists (1.24%) in the diabetic group and seven (0.6%) in the non-diabetic group exhibited recurrence (p = 0.325). CONCLUSION: The mini-open CTR with the Paine retinaculotome in diabetic patients didn't show significantly higher recurrence rate than that in non-diabetic patients in the long term.

Knockdown of SLC41A1 magnesium transporter promotes mineralization and attenuates magnesium inhibition during osteogenesis of mesenchymal stromal cells.

BACKGROUND: Magnesium is essential for numerous physiological functions. Magnesium exists mostly in bone and the amount is dynamically regulated by skeletal remodeling. Accelerating bone mass loss occurs when magnesium intake is insufficient; whereas high magnesium could lead to mineralization defects. However, the underlying magnesium regulatory mechanisms remain elusive. In the present study, we investigated the effects of high extracellular magnesium concentration on osteogenic differentiation of mesenchymal stromal/stem cells (MSCs) and the role of magnesium transporter SLC41A1 in the mineralization process. METHODS: Murine MSCs derived from the bone marrow of BALB/c mouse or commercially purchased human MSCs were treated with osteogenic induction medium containing 5.8 mM magnesium chloride and the osteogenic differentiation efficiency was compared with that of MSCs in normal differentiation medium containing 0.8 mM magnesium chloride by cell morphology, gene expression profile of osteogenic markers, and Alizarin Red staining. Slc41a1 gene knockdown in MSCs was performed by siRNA transfection using Lipofectamine RNAiMAX, and the differentiation efficiency of siRNA-treated MSCs was also assessed. RESULTS: High concentration of extracellular magnesium ion inhibited mineralization during osteogenic differentiation of MSCs. Early osteogenic marker genes including osterix, alkaline phosphatase, and type I collagen were significantly downregulated in MSCs under high concentration of magnesium, whereas late marker genes such as osteopontin, osteocalcin, and bone morphogenetic protein 2 were upregulated with statistical significance compared with those in normal differentiation medium containing 0.8 mM magnesium. siRNA treatment targeting SLC41A1 magnesium transporter, a member of the solute carrier family with a predominant Mg2+ efflux system, accelerated the mineralization process and ameliorated the inhibition of mineralization caused by high concentration of magnesium. High concentration of magnesium significantly upregulated Dkk1 gene expression and the upregulation was attenuated after the Slc41a1 gene was knocked down. Immunofluorescent staining showed that Slc41a1 gene knockdown promoted the translocation of phosphorylated ß-catenin into nuclei. In addition, secreted MGP protein was elevated after Slc41a1 was knocked down. CONCLUSIONS: High concentration of extracellular magnesium modulates gene expression of MSCs during osteogenic differentiation and inhibits the mineralization process. Additionally, we identified magnesium transporter SLC41A1 that regulates the interaction of magnesium and MSCs during osteogenic differentiation. Wnt signaling is suggested to be involved in SLC41A1-mediated regulation. Tissue-specific SLC41A1 could be a potential treatment for bone mass loss; in addition, caution should be taken regarding the role of magnesium in osteoporosis and the design of magnesium alloys for implantation.

Indocyanine green-platinum porphyrins integrated conjugated polymer hybrid nanoparticles for near-infrared-triggered photothermal and two-photon photodynamic therapy.

A type of polymeric nanoparticles loading indocyanine green and Pt(ii)-porphyrins (ICG-Pt-NPs) is constructed to achieve a synergistic effect of combined photothermal and two-photon activated photodynamic therapy. The nanoparticle core comprises the photosensitizer Pt(ii)-porphyrins (PtTFPP), and organic semiconducting polymer (PFO) that acts as a two-photon antenna. Negative ICG molecules, an NIR-absorbing photothermal dye, can be loaded into the positively charged poly-l-lysine (PLL) shell of the polymeric nanoparticles via electrostatic interaction. In these carefully designed ICG-PtTFPP integrated nanoparticles, PtTFPP absorbs the photonic energy transferred by the PFO polymer under two-photon laser excitation at 740 nm to induce photodynamic cancer cell death, while ICG offers nanoparticles a strong photothermal performance under 808 nm laser irradiation. Compared with photodynamic therapy or photothermal therapy alone, the combined therapy had a significantly synergistic effect and improved the therapeutic efficacy with near-infrared irradiation.