Sulfur is not normally considered a light‐emitting material, even though there have been reports of a dim luminescence of this compound in the blue‐to‐green spectral region. Now, it is shown how to ...make red‐emissive sulfur by a two‐step oxidation approach using elemental sulfur and Na2S as starting materials, with a high photoluminescence quantum yield of 7.2 %. Polysulfide is formed first and is partially transformed into Na2S2O3 in the first step, and then turns back to elemental S in the second step. The elevated temperature and relatively oxygen‐deficient environment during the second step transforms Na2S2O3 into Na2SO3 incorporated with oxygen vacancies, thus resulting in the formation of a solid‐state powder consisting of elemental S embedded in Na2SO3. It shows aggregation‐induced emission properties, attributed to the influence of oxygen vacancies on the emission dynamics of sulfur by providing additional lower energy states that facilitate the radiative relaxation of excitons.
Red‐emissive sulfur was synthesized through a two‐step oxidation strategy using elemental sulfur and Na2S as starting materials. It possesses aggregation‐induced emission properties attributed to the presence of oxygen vacancies providing additional energy states in the red spectral region.
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The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin ...(SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy.
We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40–60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40–60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546.
Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5–56·3) in the adjuvant-CapOx group, 56·5% (51·0–61·7) in the adjuvant-SOX group, and 59·4% (53·8–64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61–0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68–1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3–4 adverse events was neutropenia (32 12% of 258 patients in the adjuvant-CapOx group, 21 8% of 249 patients in the adjuvant-SOX group, and 30 10% of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported.
Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer.
National Key Research and Development Program of China, Beijing Scholars Program 2018–2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical.
For the Chinese translation of the abstract see Supplementary Materials section.
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Oligodendrocytes (OLs) are the myelinating glia of the central nervous system. Injury to OLs causes myelin loss. In demyelinating diseases, such as multiple sclerosis, the remyelination is hindered ...principally due to a failure of the oligodendrocyte precursor cells (OPCs) to differentiate into mature OLs. To identify inducers of OPC to OL differentiation, a high‐throughput screening based on myelin basic protein expression using neural progenitor cells‐derived OPCs has been performed and, PD0325901—an MEK (MAPK kinase) inhibitor—is found to significantly enhance OPC to OL differentiation in a dose‐ and time‐dependent manner. Other MEK inhibitors also display similar effect, indicating blockade of MAPK–ERK signaling is sufficient to induce OPC differentiation into OLs. PD0325901 facilitates the formation of myelin sheaths in OPC–neuron co‐culture in vitro. And in experimental autoimmune encephalomyelitis model and cuprizone‐induced demyelination model, PD0325901 displays significant therapeutic effect by promoting myelin regeneration. Our results suggest that targeting the MAPK–ERK pathway might be an intriguing way to develop new therapies for demyelinating diseases.
Main Points
MEK inhibitors, represented by PD0325901, promote oligodendrocyte generation.
PD0325901 promotes myelin formation both in vitro and in vivo.
The MAPK‐ERK pathway might be an intriguing target to develop new therapies for demyelinating diseases.
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The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute ...respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein
show promise therapeutically and are being evaluated clinically
. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies
in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs
. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2.
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IMPORTANCE: Laparoscopic distal gastrectomy and neoadjuvant chemotherapy are increasingly used to treat locally advanced gastric cancer. However, the safety and efficacy of the laparoscopic procedure ...after neoadjuvant chemotherapy remain unclear. OBJECTIVE: To evaluate the short-term outcomes of patients with locally advanced gastric cancer who received either laparoscopic distal gastrectomy or open distal gastrectomy. DESIGN, SETTING, AND PARTICIPANTS: Between April 23, 2015, and November 16, 2017, a phase 2, open-label, noninferiority randomized clinical trial was conducted at the Gastrointestinal Cancer Center of Peking University Cancer Hospital and Institute in Beijing, China. Patients (n = 96) between 18 and 80 years of age with locally advanced gastric cancer (cT2-4aN+M0) who were receiving neoadjuvant chemotherapy were enrolled and randomized. An as-treated population and a modified intention-to-treat (mITT) population were defined for the data analysis. INTERVENTIONS: Patients were randomized to undergo either laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy or open distal gastrectomy (ODG) with D2 lymphadenectomy. MAIN OUTCOMES AND MEASURES: The primary end point was 3-year recurrence-free survival rate. Secondary end points were surgical radicality, 30-day postoperative morbidity and mortality, 2-week postoperative recovery indexes, and adjuvant chemotherapy completion status. RESULTS: In total, 95 patients were eligible for as-treated analyses (LADG: 45, of whom 13 were female 29%, with a median interquartile range (IQR) age of 59 52-65 years; ODG: 50, of whom 16 were female 32%, with a median IQR age of 61 55-64 years) and mITT analyses (LADG: 47, of whom 14 were female 30%, with a median IQR age of 59 52-65 years; ODG: 48, of whom 15 were female 31%, with a median IQR age of 61 55-64 years). In the as-treated analyses, the LADG group had a significantly lower postoperative complication rate than the ODG group (20% vs 46%; P = .007). The postoperative visual analog scale score for pain was 1.2 units lower on postoperative day 2 only in the LADG group (95% CI, −2.1 to −0.3; P = .008). Patients in the LADG group had better adjuvant chemotherapy completion (adjusted odds ratio, 4.39; 95% CI, 1.63-11.80; P = .003) and were less likely to terminate adjuvant chemotherapy because of adverse effects (10 22% vs 21 42%; P = .04). The mITT analyses showed similar results to as-treated analyses. CONCLUSIONS AND RELEVANCE: This trial found that LADG appears to offer the benefits of better postoperative safety and adjuvant chemotherapy tolerance compared with ODG for patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02404753
Oligodendrocyte‐formed myelin sheaths play important roles in the neuronal functions in the central nervous system. In demyelinating diseases, such as Multiple Sclerosis, the myelin sheaths are ...damaged and the remyelinating process is somehow hindered. Restoration of the myelin sheaths requires the differentiation of the oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). To discover small molecule compounds that might promote the OPC to OL differentiation, a high‐throughput screening system is established and L‐ascorbyl‐2‐phosphate (As‐2P), a stable form of Vitamin C (Vc), is found to greatly enhance the OPC to OL differentiation. As‐2P promotes gradual expression of OL lineage markers, including O4, CNPase and MBP, in a dose‐ and time‐dependent manner. It also facilitates the formation of myelin sheaths in OPC‐neuron co‐culture. As‐2P also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone‐mediated demyelination animal model. Interestingly, As‐2P's function in promoting OPC differentiation is not related to its antioxidant activity. And an intracellular rather than an extracellular mechanism might be involved. Considering the safe use of Vc as a dietary supplement for many years, it might also be used as an alternative medicine for CNS demyelinating diseases.
Main Points
As‐2P, a stable form of Vitamin C, promotes oligodendrocyte differentiation.
As‐2P promotes myelin formation both in vitro and in vivo.
SVCT2 mediates As‐2P's effect in oligodendrocyte differentiation.
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•Electron Zeeman interaction axis is tilted with respect to the external magnetic field.•Nuclear Zeeman interaction has a component orthogonal to the quantization axis of the electron ...spin.•Orthogonal component of the nuclei is responsible for an additional mechanism of coherence formation.•ESEEM signal can be formed even in the case of a purely isotropic super-HFI interaction.
The anisotropic Zeeman and strong hyperfine interactions of a Kramers ion can significantly affect its magnetic properties as well as the interactions with the nearby nuclei. The interactions with the local environment are described in the preceding article. In the current work, the change of the spin states of distant nuclei is studied. Analytical expressions describing the depth of the electron spin echo envelope modulation (ESEEM) are obtained for the ions with anisotropic Zeeman and strong hyperfine interactions. Due to the g-tensor anisotropy, the electron Zeeman interaction axis is tilted in respect to the direction of the external magnetic field which makes non-collinear with the Zeeman interaction axes of the ion and the nearby nuclei and significantly modifies the nuclear spin states. Thus, the isotropic hyperfine interaction, and particularly the Fermi contact interaction can directly contribute to the ESEEM. An additional factor, that can significantly modify the ESEEM signal is the mixing of the multiple oscillations arising when several nuclei occur in optimal conditions for the generation of the nuclear coherence. This situation arises when several EPR transitions of the ion covering a wide range of magnetic fields are examined.
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Sulfur nanodots (S-dots), composed of an elemental sulfur core and surface ligands, show unexpected photoluminescence (PL) properties, with the unique features of nontoxicity, hydrophilicity, high ...stability and easy modification. This review systematically introduces the synthesis methods, characterization, PL mechanisms and some typical applications of S-dots in chemical sensing. As the PL quantum yield (QY) is a key factor to evaluate the performance of luminescent materials, we report the synthesis methods according to the achievement in the promotion of PL QY. The PL mechanisms of S-dots are discussed from the view of the effects of the elemental sulfur core and passivated ligands on the PL QY and emission color. The design principle of analytical methods for various target molecules using S-dots is introduced. We end this review with the conclusions and some challenges in this field, which is expected to provide some clues for researchers in this field.
This review systematically introduces the synthesis methods, characterization, PL mechanisms and some typical applications of S-dots in chemical sensing.
An ultrasonication-promoted strategy was proposed to synthesize luminescent S-dots, which reduced the synthesis time from the commonly used 5 days to several hours. The as-synthesized S-dots show a ...high photostability and low cytotoxicity, and are then successfully applied for cellular imaging.
An ultrasonication-promoted strategy was proposed to synthesize luminescent sulfur nanodots, reducing the synthesis time from 5 days to several hours.
Developing solid luminescent materials with a unity quantum yield and tunable emission color is promising, although it is still a difficult task. A straightforward heat‐treatment method has been ...developed to load 3,4,9,10‐perylenetetracarboxylic dianhydride (PTCDA) into the matrix of boric acid (BA) to produce powders with a near‐unity quantum yield and tunable emission color from yellow to green. Our results suggest that the emission of the powders originates from PTCDA, and the tunability of the emission color is caused by the hydrolysis of PTCDA in the alkaline environment. The near‐unity quantum yield is attributed to the BA matrix, which confines PTCDA. In addition, the powder also shows excellent thermal stability that allows its application in light‐emitting diodes. The above results are important for the development of solid‐state luminescent materials for various applications, and also provide a clue for studying the emission properties of luminescent materials.
A straightforward heat‐treatment strategy is proposed to load 3,4,9,10‐perylenetetracarboxylic dianhydride into the matrix of boric acid to produce powders with a near‐unity quantum yield and tunable emission color from yellow to green. The confinement effect of boric acid is responsible for the high emission efficiency of products.
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