The development of an extensive toolkit for potential point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect SARS-CoV-2. Herein, we outline the development of an alternative CRISPR nucleic acid diagnostic utilizing a Cas13d ribonuclease derived from Ruminococcus flavefaciens XPD3002 (CasRx) to detect SARS-CoV-2, an approach we term SENSR (sensitive enzymatic nucleic acid sequence reporter) that can detect attomolar concentrations of SARS-CoV-2. We demonstrate 100% sensitivity in patient-derived samples by lateral flow and fluorescence readout with a detection limit of 45 copy/μL. This technology expands the available nucleic acid diagnostic toolkit, which can be adapted to combat future pandemics.

The aim of the present study was to verify the potential association between multiple myeloma (MM) and hepatitis B/C virus (HBV/HCV) infection. This retrospective case-control trial included 299 patients with MM and 299 patients with acute leukemia (AL). Age and sex were matched between the two groups. The hepatitis B surface antigen (HBsAg) positivity rate was significantly higher in the MM group (19.4% vs. 12.0% in patients with AL; p = 0.014). The rate of HCV infection did not differ between the two groups. The incidence of cirrhosis was significantly higher in HBsAg+ patients (17.2% vs. 6.2% in HBsAg- patients; p = 0.011). The rate of hepatitis E virus (HEV) infection was also significantly higher in HBsAg+ patients (5.2% vs. 0.4% in HBsAg- patients; p = 0.025). Hepatic damage was much more common in HBsAg+ patients than in HBsAg- patients both prior to (22.4% vs. 8.7%; p = 0.006) and during chemotherapy for MM (67.2% vs. 28.6%; p < 0.001). ISS stage, HBsAg+, the use of bortezomib and thalidomide and autologous stem cell transplant were significant factors for overall survival in univariate analysis. In the Cox regression analysis, ISS stage (p = 0.027), HBsAg+ (p = 0.042) and the use of thalidomide (p = 0.001) showed a significant effect on the OS of these patients. The prevalence of HBV infection is higher in patients with MM than in subjects with other hematological malignancies such as AL. Hepatic injury is more common in patients with MM with HBV infection, particularly during chemotherapeutic treatment. HBsAg positivity may be a prognosis factor in patients with MM in HBV endemic areas.

Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. Here, to overcome this challenge, we engineer SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species), an engineered genetic incompatibility approach, to generate postzygotic reproductive barriers. Using this approach, we create multiple reproductively isolated SPECIES and demonstrate their reproductive isolation and threshold-dependent gene drive capabilities in D. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.

To investigate hepatitis B virus (HBV) reactivation and survival in patients with multiple myeloma (MM) receiving bortezomib-containing regimens, we analyzed 139 patients with MM receiving bortezomib-containing regimens in our hospital. Twenty-seven/139 patients were hepatitis B surface antigen positive (HBsAg+) with nine having DNA levels > 500 IU/mL, including four > 1000 IU/mL. All but five HBsAg+ patients were treated with lamivudine or entecavir before chemotherapy until at least 6 months after chemotherapy or autologous stem cell transplant (ASCT). HBV reactivation occurred in six HBsAg+ patients and two HBsAg- patients, including six who received ASCT. Overall survival and progression-free survival of HBsAg- patients were significantly longer than for HBsAg+ patients (both p < 0.01). From these results, we confirmed that the incidence of HBV reactivation was notable in patients with MM receiving bortezomib-containing regimens, especially those who underwent ASCT. HBsAg+ patients with MM had a poorer prognosis than HBsAg- patients. Prophylactic treatment should be prescribed to all patients with HBsAg+ MM for a minimum duration of 12 months.

A rationally designed near-infrared two-photon fluorescent probe (SDP-A) for selectively detecting cysteine (Cys) has been developed based on a newly designed conjugation-enhanced 2-(2′hydroxyphenyl)benzothiazole derivative as the fluorophore, an acrylate moiety as the Cys reaction site, and an N-methylpyridinium scaffold as both the unit of organelle targeting and improving water solubility. The probe SDP-A alone essentially emitted no fluorescence, whereas it achieved a superb near-infrared fluorescence emission (713 nm) enhancement within 15 min with a significant Stokes shift (302 nm) in the presence of Cys. The photoluminescence mechanism of the probe SDP-A toward Cys was modulated by excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) processes. It exhibited high selectivity and sensitivity (LOD = 102 nM) for monitoring Cys over other analytes such as Hcy/GSH/H 2 S owing to a specific conjugate addition−cyclization reaction between Cys and the acrylate moiety. More importantly, the released fluorophore SDP exhibits elevated quantum yields (1.52−18.17%) in different solvents and strong two-photon excited fluorescence with a sizeable two-photon action cross-section (Φ) of 213.5 GM at 820 nm in acetonitrile−PBS medium, which is highly desirable for two-photon fluorescence imaging of the living samples. Therefore, SDP-A was successfully applied to the imaging of Cys in live cells, zebrafish, mouse brain, and abdominal cavity down to a depth of more than 200 μm using a one/two-photon fluorescence microscope.

We have developed a generalizable strategy to quantify the effect of surface barriers on zeolite catalysis. Isomerization of n‐pentane, catalyzed by Pt/Beta, is taken as a model reaction system. Firstly, the surface modification by chemical liquid deposition of SiO2 was carried out to control the surface barriers on zeolite Beta crystals. The deposition of SiO2 leads to a very slight change in the physical properties of Beta crystals, but an obvious reduction in Brønsted acid sites. Diffusion measurements by the zero‐length column (ZLC) method show that the apparent diffusivity of n‐pentane can be more than doubled after SiO2 deposition, indicating that the surface barriers have been weakened. Catalytic performance was tested in a fixed‐bed reactor, showing that the apparent catalytic activity improved by 51–131 % after SiO2 deposition. These results provide direct proof that reducing surface barriers can be an effective route to improve zeolite catalyst performance deteriorated by transport limitations.

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Many questions about minimal residual disease (MRD) still need to be answered for multiple myeloma (MM). Flow MRD was monitored in 104 consecutive patients with MM after induction and at the 3rd, 6th, 9th, 12th, 18th, and 24th months post-transplant. Four MRD evolution patterns were revealed: Pattern 1 patients had persistent MRD-negative status after post-induction with no progression; pattern 2 patients had MRD-positive status postinduction but became MRD negative within 24 months post-transplant; pattern 3 patients had MRD-negative status postinduction but became MRD positive within 24 months post-transplant; and pattern 4 patients had persistent MRD-positive status after postinduction. Patients with MRD evolution pattern 1 had a better time to progression than did patients with the other evolution patterns (not reached versus not reached, versus 15.4 ± 2.4 months, versus 16.9 ± 3.0 months; log-rank test, P = .003, P = .000, and P = .000, respectively). Patients with MRD pattern 1 had a significantly longer overall survival than did patients with pattern 3 (not reached versus 35.2 ± 18.6 months; log-rank test, P = .000) and pattern 4 (not reached versus 23.8 ± 15.0 months, log-rank test, P = .000) but had a similar overall survival as pattern 2 patients (not reached versus not reached; log-rank test, P = .229). For progressing patients with MRD evolution pattern 2 or 3, the median interval of a sustained MRD-negative status was only 17 months and the median time from MRD reappearance to disease progression was only 4.6 months. A more complete MRD evolution pattern was developed to predict the outcomes for patients with MM. The optimal time of MRD assessment should include postinduction and 3rd and 24th month post-transplant. Regular MRD assessments will help detect relapse early. A sustained negative MRD status should last for at least 24 months.