Single-cell analysis via manifold fitting: A framework for RNA clustering and beyond.

Single-cell RNA sequencing (scRNA-seq) data, susceptible to noise arising from biological variability and technical errors, can distort gene expression analysis and impact cell similarity assessments, particularly in heterogeneous populations. Current methods, including deep learning approaches, often struggle to accurately characterize cell relationships due to this inherent noise. To address these challenges, we introduce scAMF (Single-cell Analysis via Manifold Fitting), a framework designed to enhance clustering accuracy and data visualization in scRNA-seq studies. At the heart of scAMF lies the manifold fitting module, which effectively denoises scRNA-seq data by unfolding their distribution in the ambient space. This unfolding aligns the gene expression vector of each cell more closely with its underlying structure, bringing it spatially closer to other cells of the same cell type. To comprehensively assess the impact of scAMF, we compile a collection of 25 publicly available scRNA-seq datasets spanning various sequencing platforms, species, and organ types, forming an extensive RNA data bank. In our comparative studies, benchmarking scAMF against existing scRNA-seq analysis algorithms in this data bank, we consistently observe that scAMF outperforms in terms of clustering efficiency and data visualization clarity. Further experimental analysis reveals that this enhanced performance stems from scAMF's ability to improve the spatial distribution of the data and capture class-consistent neighborhoods. These findings underscore the promising application potential of manifold fitting as a tool in scRNA-seq analysis, signaling a significant enhancement in the precision and reliability of data interpretation in this critical field of study.

Ring-shaped cavity anchor Pt to derive Pt/WO3-x heterointerfaces for efficient hydrogen evolution in acidic water and seawater.

Developing novelplatinum (Pt)-based hydrogen evolution reaction (HER) catalysts with high activity and stability is significant for the ever-broader applications of hydrogen energy. However, achieving precise modulation of the ultrafine Pt nanoparticles coordination environment in conventional catalysts is challenging. In this work, we developed a unique "ring-shaped cavity induced" strategy to anchor the Ptx through the ring-shaped cavity of polyoxometalates (POMs) Na33H7P8W48O184 (denoted as P8W48). The NayPtx[P8W48O184] (PtxP8W48) was in-situ converted into abundant Pt/WO3-x heterostructure with Pt (∼2 nm) and highly depressed Pt-O-W heterointerfaces. Pt/WO3-x nanoparticles supported on highly conductive rGO exhibit superior HER activity. The overpotentials of the catalyst are only 2.8 mV and 4.7 mV at 10 mA·cm-2 in acidic water and seawater, far superior to commercial 20 % Pt/C catalyst. Additionally, the catalyst can be stabilized at a current density of 30 mA·cm-2 for 180 h. This study provides a feasible strategy for rational design of Pt-based catalysts for renewable energy applications.

Precise Pore Engineering of Zirconium Metal-Organic Cages for One-Step Ethylene Purification from Ternary Mixtures.

One-step purification of ethylene from ternary mixtures (C2H2, C2H4, and C2H6) can greatly reduce the energy consumption of the separation process, but it is extremely challenging. Herein, we use crystal engineering and reticular chemistry to introduce unsaturated bonds (ethynyl and alkyne) into ligands, and successfully design and synthesized two novel Zr-MOCs (ZrT-1-ethenyl and ZrT-1-alkyne). The introduction of carbon-carbon unsaturated bonds provides abundant adsorption sites within the framework while modulating the pore window size. Comprehensive characterization techniques including single crystal and powder X-ray diffraction, as well as electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) confirm that ZrT-1-ethenyl and ZrT-1-alkyne possess an isostructural framework with ZrT-1 and ZrT-1-Me, respectively. Adsorption isotherms and breakthrough experiments combined with theoretical calculations demonstrate that ZrT-1-ethenyl can effectively remove trace C2H2 and C2H6 in C2H4 and achieve separation of C2H2 from C2H4 and CO2. ZrT-1-ethenyl can also directly purify C2H4 in liquid solutions. This work provides a benchmark for MOCs that one-step purification of ethylene from ternary mixtures.

Atomic physics on a 50-nm scale: Realization of a bilayer system of dipolar atoms.

Controlling ultracold atoms with laser light has greatly advanced quantum science. The wavelength of light sets a typical length scale for most experiments to the order of 500 nanometers (nm) or greater. In this work, we implemented a super-resolution technique that localizes and arranges atoms on a sub-50-nm scale, without any fundamental limit in resolution. We demonstrate this technique by creating a bilayer of dysprosium atoms and observing dipolar interactions between two physically separated layers through interlayer sympathetic cooling and coupled collective excitations. At 50-nm distance, dipolar interactions are 1000 times stronger than at 500 nm. For two atoms in optical tweezers, this should enable purely magnetic dipolar gates with kilohertz speed.

Ultrafine Co-MoC particles in porous carbon derived from polyoxometalate-based metal organic framework for efficient hydrogen evolution reaction.

Accurately regulating ultrafine molybdenum carbide (MoC)-based catalysts is a significant challenge in the rational design of hydrogen evolution reaction (HER) electrocatalysts. Herein, under the guidance of the first principle calculations, we proposed an in-situ polyoxometalate-confined strategy for creating uniformly distributed ultrafine Co-MoC bimetallic nanoparticles in porous carbon nanostars, with the assistance of precisely designed metal-organic framework (MOF). The Co-MoC@C electrocatalyst has a high specific surface area of 969 m2·g-1 because of the conductive carbon substrate with abundant mesopores, which makes for exposing more active sites of Co-MoC nanocrystals (∼1.5 nm) and facilitating electron/ion transport. Thus, Co-MoC@C electrocatalyst shows the excellent electrochemical activity with overpotentials of 88.4 mV and 66.6 mV at a current density of 10 mA·cm-2 under acidic and alkaline conditions, respectively. The in-situ polyoxometalate-confined strategy will provide a new guideline for the design and preparation of efficient HER electrocatalysts.

In Situ Rapid-Formation Sprayable Hydrogels for Challenging Tissue Injury Management.

Rapid-acting, convenient, and broadly applicable medical materials are in high demand for the treatment of extensive and intricate tissue injuries in extremely medical scarcity environment, such as battlefields, wilderness, and traffic accidents. Conventional biomaterials fail to meet all the high criteria simultaneously for emergency management. Here, a multifunctional hydrogel system capable of rapid gelation and in situ spraying, addressing clinical challenges related to hemostasis, barrier establishment, support, and subsequent therapeutic treatment of irregular, complex, and urgent injured tissues, is designed. This hydrogel can be fast formed in less than 0.5 s under ultraviolet initiation. The precursor maintains an impressively low viscosity of 0.018 Pa s, while the hydrogel demonstrates a storage modulus of 0.65 MPa, achieving the delicate balance between sprayable fluidity and the mechanical strength requirements in practice, allowing flexible customization of the hydrogel system for differentiated handling and treatment of various tissues. Notably, the interactions between the component of this hydrogel and the cell surface protein confer upon its inherently bioactive functionalities such as osteogenesis, anti-inflammation, and angiogenesis. This research endeavors to provide new insights and designs into emergency management and complex tissue injuries treatment.

Fabrication of highly dispersed Pd-Mn3O4 catalyst for efficient catalytic propane total oxidation.

Adjusting the interaction between dual active components for enhancing volatile organic compounds (VOCs) degradation is an effective but still challenging means of air pollution control. Herein, a limited pyrolysis oxidation strategy was adopted to prepare Pd-Mn3O4 spinel catalysts with uniform morphology and active component dispersion. Among these, 1.08Pd-Mn3O4 presented the highest catalytic efficiency with a T90 value of 240 °C, which was 94 °C lower than that of Mn3O4. Characterization and density functional theory (DFT) calculation results revealed that the strong metal-support interaction (SMSI) effect between Pd and Mn3O4 promoted the redistribution of surface charges, thus strengthening the oxidation-reduction ability of the active sites. Moreover, the SMSI effect led to a better migration of surface oxygen species, and boosted the generation of active surface oxygen species. Simultaneously, the Pd catalyst further reduced the energy barrier in the initial stage of the dehydrogenation of propane. Overall, this study provided a novel design strategy for dual active components catalysts with SMSI effect and extended the application of these catalysts in the important field of VOCs elimination.

Rechallenge with EGFR-TKI after failure of immunotherapy is considered an effective treatment for advanced lung adenocarcinoma patients with EGFR exon 19 deletion: a case report.

In advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have an excellent and long-lasting therapeutic response; however, virtually all patients eventually develop drug resistance and experience disease progression. The use of immunotherapy after EGFR-TKIs may be a successful therapeutic option for individuals who are resistant to them. It is still unclear if EGFR-TKIs can be administered again after immunotherapy has failed. We describe a case of a 37-year-old woman who was found to have T4N3M1a stage IVa lung adenocarcinoma. Amplification refractory mutation system PCR (ARMS-PCR) genetic testing suggested EGFR exon 19 deletion. The patient was initially treated with a regimen of icotinib (125 mg tid) combined with anlotinib (8 mg qd d1-d14) with an optimal efficacy rating of partial response (PR) and was granted a PFS of 7 months. In second-line treatment, the patient received three cycles of a KN046 (KN046 is a bispecific antibody inhibitor of PD-L1 and CTLA-4) 295 mg d1, pemetrexed 800 mg d1, plus carboplatin 750 mg d1 regimen, with an optimal efficacy rating of stable disease (SD) on CT. The third-line therapy was chosen to be afatinib with docetaxel, and the patient was evaluated for PR on CT. Up to 15 August 2022, the patient had a progression free survival (PFS) of 14 months. The successful treatment of this patient is a reminder that EGFR-TKI rechallenge in EGFR exon 19 deletion patients with EGFR-TKI resistance, in which immunotherapy has failed, may be effective.

From atomic bonding to heterointerfaces: Co2P/WC constructed by lacunary polyoxometalates induced strategy as efficient hydrogen evolution electrocatalysts at all pH values.

Herein, a novel in-situ "atomic binding to heterointerface" strategy is proposed to obtain Co2P/WC@NC/CNTs catalyst with abundant heterointerface between cobalt phosphide and tungsten carbide (Co2P/WC) by the polyoxometalates (POMs)-based metal-organic frameworks (MOFs) precursor. The natural quasi interfaces in K10[Co4(H2O)2(PW9O34)2] molecule crucially guide the abundant Co2P/WC heterointerfaces down to atomic level. Meanwhile, MOFs cages can effectively encapsulate nanosized POMs at molecular level to control the size and dispersion of Co2P/WC nanoparticle, while carbon nanotubes (CNTs) enhance conductivity at nanoscale level. The interfacial electronic modulation between Co2P and WC lowering the energy barrier of the rate determining step, thus Co2P/WC@NC/CNTs showed reasonable hydrogen evolution reaction (HER) activity and stability in all-pH media including sea water. This work provides a "bottom-up" synthetic strategy for confined heterostructures, thus offering the prospect for more efficient interfacial charge modulation.

Lacunary polyoxometalate oriented construction of dispersed Ni3S2 confined in WO3 for electrocatalytic water splitting.

Manufacturing low-cost, high-performance and earth-rich catalysts for hydrogen evolution (HER) and oxygen evolution reactions (OER) is critical to achieving sustainable green hydrogen production. Herein, we utilize lacunary Keggin-structure [PW9O34]9- (PW9) as a molecular pre-assembly platform to anchor Ni within a single PW9 molecule by vacancy-directed and nucleophile-induced effects for the uniform dispersion of Ni at the atomic level. The chemical coordination of Ni with PW9 can avoid the aggregation of Ni and favor the exposure of active sites. The Ni3S2 confined by WO3 prepared from controlled sulfidation of Ni6PW9/Nickel Foam (Ni6PW9/NF) exhibited excellent catalytic activity in both 0.5 M H2SO4 and 1 M KOH solutions, which required only 86 mV and 107 mV overpotentials for HER at a current density of 10 mA∙cm-2 and 370 mV for OER at 200 mA∙cm-2. This is attributed to the good dispersion of Ni at the atomic level induced by trivacant PW9 and the enhanced intrinsic activity by synergistic effect of Ni and W. Therefore, the construction of active phase from the atomic level is insightful to the rational design of dispersed and efficient electrolytic catalysts.

Clinical efficacy of ultrasound-guided interventional therapy in patients with benign ovarian cysts: a meta-analysis.

This study aimed to explore the clinical efficacy of ultrasound-guided interventional therapy in patients with benign ovarian cysts through meta-analysis. A literature search was performed on PubMed, Web of Science, Embase, CNKI, and WanFang databases to obtain clinical randomized controlled trials on ultrasound-guided interventional therapy for benign ovarian cysts published between 2010 and 2022. A total of 1395 studies were initially retrieved, and finally 12 studies were included for meta-analysis. The results showed that the observation group (ultrasound-guided interventional therapy) had higher treatment effective rate than the control group (conventional laparotomy or laparoscopic cyst resection), but the incidence of adverse reactions was markedly lower. Additionally, the length of hospital stay, intraoperative blood loss, and operation time showed significant lower levels in the observation group. In terms of ovarian function, postoperative luteinizing hormone and follicle-stimulating hormone levels in the observation group were lower than the control group, while oestradiol levels were higher. In conclusion, compared with conventional surgical treatment, ultrasound-guided interventional therapy can significantly improve the clinical effective rate, shorten the hospital stay and reduce intraoperative blood loss. Such therapy can protect ovarian reserve, with high value of clinical promotion.IMPACT STATEMENTWhat is already known on this subject? Main surgical methods for ovarian cysts consist of laparotomy, laparoscopic surgery, and interventional therapy.What the results of this study add? With the advancement of surgical techniques and instruments, many minimally invasive surgeries have been applied to treat ovarian cysts with good clinical results. However, there is no exact evidence to prove its clinical efficacy. Given the lack in this field, we conducted a meta-analysis of all clinical studies of ultrasound-guided interventional therapy for ovarian cysts to evaluate its efficacy and safety.What the implications are of these findings for clinical practice and/or further research? Compared with conventional laparotomic or laparoscopic cyst resection, ultrasound-guided interventional therapy for ovarian cysts significantly improves the treatment effectiveness, shortens the hospital stay and reduces intraoperative blood loss. This therapy with good clinical efficacy also has advantages of small wound, rapid recovery and less adverse reactions, and can protect ovarian reserve. This safe and effective surgical method for ovarian cysts is worth promoting clinically.

Urea-H2O2 defect engineering of δ-MnO2 for propane photothermal oxidation: Structure-activity relationship and synergetic mechanism determination.

Photothermal catalysis has an advantage in effective and economical elimination technology of volatile organic compounds (VOCs) in the ascendant. Herein, various surface defect engineering routes were adopted to enhance the low-temperature propane oxidation of δ-MnO2. Compared to reducing etchants urea and vitamin C, δ-MnO2 treated with urea - H2O2 exhibited an excellent thermal (T90 = 240 ℃) and photothermal (T90 = 196 ℃) activities of propane oxidation. Urea - H2O2 treatment provided high concentration of Mn4+ and surface-active oxygen (Mn4+-Osur) species as surface-active sites, and produced numerous oxygen vacancies to improve charge separation and superoxide species generation capacity. Thus, the photothermal conversion efficiency and low-temperature reducibility were remarkably enhanced. Furthermore, the photothermal synergistic catalytic mechanism was proposed based on in-situ diffuse reflectance infrared Fourier transform spectroscopy and control experiments. The strategy here offered insight into the rational design of efficient transition catalysts, and in-depth understanding of the photothermal catalytic VOCs removal mechanism.

Diverse effects of gaze direction on heading perception in humans.

Gaze change can misalign spatial reference frames encoding visual and vestibular signals in cortex, which may affect the heading discrimination. Here, by systematically manipulating the eye-in-head and head-on-body positions to change the gaze direction of subjects, the performance of heading discrimination was tested with visual, vestibular, and combined stimuli in a reaction-time task in which the reaction time is under the control of subjects. We found the gaze change induced substantial biases in perceived heading, increased the threshold of discrimination and reaction time of subjects in all stimulus conditions. For the visual stimulus, the gaze effects were induced by changing the eye-in-world position, and the perceived heading was biased in the opposite direction of gaze. In contrast, the vestibular gaze effects were induced by changing the eye-in-head position, and the perceived heading was biased in the same direction of gaze. Although the bias was reduced when the visual and vestibular stimuli were combined, integration of the 2 signals substantially deviated from predictions of an extended diffusion model that accumulates evidence optimally over time and across sensory modalities. These findings reveal diverse gaze effects on the heading discrimination and emphasize that the transformation of spatial reference frames may underlie the effects.

A Feshbach resonance in collisions between triplet ground-state molecules.

Collisional resonances are important tools that have been used to modify interactions in ultracold gases, for realizing previously unknown Hamiltonians in quantum simulations1, for creating molecules from atomic gases2 and for controlling chemical reactions. So far, such resonances have been observed for atom-atom collisions, atom-molecule collisions3-7 and collisions between Feshbach molecules, which are very weakly bound8-10. Whether such resonances exist for ultracold ground-state molecules has been debated owing to the possibly high density of states and/or rapid decay of the resonant complex11-15. Here we report a very pronounced and narrow (25 mG) Feshbach resonance in collisions between two triplet ground-state NaLi molecules. This molecular Feshbach resonance has two special characteristics. First, the collisional loss rate is enhanced by more than two orders of magnitude above the background loss rate, which is saturated at the p-wave universal value, owing to strong chemical reactivity. Second, the resonance is located at a magnetic field where two open channels become nearly degenerate. This implies that the intermediate complex predominantly decays to the second open channel. We describe the resonant loss feature using a model with coupled modes that is analogous to a Fabry-Pérot cavity. Our observations provide strong evidence for the existence of long-lived coherent intermediate complexes even in systems without reaction barriers and open up the possibility of coherent control of chemical reactions.

CCK regulates osteogenic differentiation through TNFα/NF-κB in peri-implantitis.

OBJECTIVE: Peri-implantitis is characterized by peri-implant mucositis and alveolar bone resorption. This study investigated cholecystokinin (CCK) expression and the mechanism underlying its involvement in peri-implantitis. METHODS: mRNA sequencing was performed using the Gene Expression Omnibus database GSE106090. Human bone marrow mesenchymal stem cells (hBMSCs) were pretreated with various concentrations of CCK (0, 10, 30, or 100 nM) for 1 hour before induction in osteogenic differentiation medium for 2 weeks. Alkaline phosphatase (ALP) activity was determined, and the cells were stained with alizarin red. The expression levels of TNFα and the osteogenic markers ALP, RUNX2, and OCN were measured using quantitative real-time PCR. TNFα, phosphorylated P65, and total P65 levels were determined by western blot. RESULTS: Compared with healthy individuals, 262 and 215 genes were up- and down-regulated, respectively, in the periodontal tissues of patients with peri-implantitis. CCK expression was significantly upregulated in patients with peri-implantitis. CCK reduced ALP activity, osteogenic differentiation, and levels of the osteogenic markers ALP, RUNX2, and OCN. Moreover, CCK promoted levels of TNFα and phosphorylated P65, which is a marker of activation for the NF-κB inflammatory pathway. CONCLUSIONS: CCK regulates osteogenic differentiation through the TNFα/NF-κB axis in peri-implantitis.

Fast-growing immature ovarian teratoma during pregnancy: a case report and a review of the literature.

BACKGROUND: Immature ovarian teratoma is one of the three common malignant ovarian germ cell tumors. However, immature ovarian teratoma in pregnancy is very rare. Due to the rare occurrence, there is little evidence regarding its diagnosis, optimal management, and prognosis. Hence, we present a case of immature teratoma diagnosed during pregnancy, and analyze its clinicopathological features, management and prognosis. CASE PRESENTATION: A 28-year-old woman underwent a sonographic examination revealed no abnormality in the bilateral adnexal area before 29 weeks gestational age (WGA). At 29 WGA, ultrasound demonstrated a 9.7 × 8.5 × 6.4 cm complex structure in the left adnexal area. At 30 WGA, repeated ultrasound revealed rapid growth of tumor mass, measuring 25.0 × 15.0 × 13.7 cm. An elective cesarean section combined with exploratory laparotomy was performed at 33 WGA. Intraoperative frozen pathological examination suggested left ovarian immature teratoma. Then, she underwent a complete staging surgery. Subsequently, the patient received 4 cycles of bleomycin-etoposide-cisplatin (BEP) chemotherapy. After 18 months of follow-up, there is no sign of tumor recurrence till now. CONCLUSIONS: This case report suggests that the benefits and risks of timely treatment for patients and fetuses should be fully assessed by a multidisciplinary team. The early diagnosis, the timing of surgery and chemotherapy, the choice of chemotherapy for BEP will determine the prognosis. Surgery and combination chemotherapy with BEP play an important role in the treatment of immature teratomas in pregnancy, and could gain successful and satisfactory outcomes for mother and fetus.

Sex and Race Differences in the Evaluation and Treatment of Young Adults Presenting to the Emergency Department With Chest Pain.

Background Acute myocardial infarctions are increasingly common among young adults. We investigated sex and racial differences in the evaluation of chest pain (CP) among young adults presenting to the emergency department. Methods and Results Emergency department visits for adults aged 18 to 55 years presenting with CP were identified in the National Hospital Ambulatory Medical Care Survey 2014 to 2018, which uses stratified sampling to produce national estimates. We evaluated associations between sex, race, and CP management before and after multivariable adjustment. We identified 4152 records representing 29 730 145 visits for CP among young adults. Women were less likely than men to be triaged as emergent (19.1% versus 23.3%, respectively, P<0.001), to undergo electrocardiography (74.2% versus 78.8%, respectively, P=0.024), or to be admitted to the hospital or observation unit (12.4% versus 17.9%, respectively, P<0.001), but ordering of cardiac biomarkers was similar. After multivariable adjustment, men were seen more quickly (hazard ratio [HR], 1.15 [95% CI, 1.05-1.26]) and were more likely to be admitted (adjusted odds ratio, 1.40 [95% CI, 1.08-1.81]; P=0.011). People of color waited longer for physician evaluation (HR, 0.82 [95% CI, 0.73-0.93]; P<0.001) than White adults after multivariable adjustment, but there were no racial differences in hospital admission, triage level, electrocardiography, or cardiac biomarker testing. Acute myocardial infarction was diagnosed in 1.4% of adults in the emergency department and 6.5% of admitted adults. Conclusions Women and people of color with CP waited longer to be seen by physicians, independent of clinical features. Women were independently less likely to be admitted when presenting with CP. These differences could impact downstream treatment and outcomes.

Control of reactive collisions by quantum interference.

In this study, we achieved magnetic control of reactive scattering in an ultracold mixture of 23Na atoms and 23Na6Li molecules. In most molecular collisions, particles react or are lost near short range with unity probability, leading to the so-called universal rate. By contrast, the Na + NaLi system was shown to have only ~4% loss probability in a fully spin-polarized state. By controlling the phase of the scattering wave function via a Feshbach resonance, we modified the loss rate by more than a factor of 100, from far below to far above the universal limit. The results are explained in analogy with an optical Fabry-Perot resonator by interference of reflections at short and long range. Our work demonstrates quantum control of chemistry by magnetic fields with the full dynamic range predicted by our models.

Pauli blocking of light scattering in degenerate fermions.

Pauli blocking of spontaneous emission is responsible for the stability of atoms. Electrons cannot decay to lower-lying internal states that are already occupied. Pauli blocking also occurs when free atoms scatter light elastically (Rayleigh scattering) and the final external momentum states are already populated. This was predicted more than 30 years ago but is challenging to realize experimentally. Here, we report on Pauli blocking of light scattering in a dense quantum-degenerate Fermi gas of ultracold lithium atoms. When the Fermi momentum is larger than the photon recoil, most final momentum states are within the Fermi surface. At low temperature, we find that light scattered even at large angles is suppressed by 37% compared with higher temperatures, where atoms scatter at the single-atom Rayleigh scattering rate.

Dirac solitons in optical microresonators.

Mode-coupling-induced dispersion has been used to engineer microresonators for soliton generation at the edge of the visible band. Here, we show that the optical soliton formed in this way is analogous to optical Bragg solitons and, more generally, to the Dirac soliton in quantum field theory. This optical Dirac soliton is studied theoretically, and a closed-form solution is derived in the corresponding conservative system. Both analytical and numerical solutions show unusual properties, such as polarization twisting and asymmetrical optical spectra. The closed-form solution is also used to study the repetition rate shift in the soliton. An observation of the asymmetrical spectrum is analysed using theory. The properties of Dirac optical solitons in microresonators are important at a fundamental level and provide a road map for soliton microcomb generation in the visible band.