Discovery of a pathway for terminal-alkyne amino acid biosynthesis.

Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction1-4. However, biologically 'rare' functional groups, such as the fluoro5, chloro6,7, bromo7,8, phosphonate9, enediyne10,11, cyano12, diazo13, alkene14 and alkyne15-17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(I)-catalysed azide-alkyne cycloaddition 'click' reaction18. Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that L-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C-C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications.

Health-related quality of life and its influencing factors in patients with primary cutaneous B-cell lymphomas: A multicentric study in 100 patients.

BACKGROUND: Primary cutaneous B-cell lymphomas (CBCL) are a group of rare malignant skin diseases that represent approximately 20%-30% of all primary cutaneous lymphomas (PCL). Previous studies revealed impaired health-related quality of life (HRQoL) in patients diagnosed with primary cutaneous T-cell lymphoma (CTCL). Currently, only small-sized studies investigated HRQoL in CBCL patients and lacked detailed analysis of respective subtypes. OBJECTIVES: This study aims to investigate HRQoL in CBCL patients to identify independent factors of HRQoL impairment in CBCL patients. METHODS: One hundred CBCL patients were recruited from eight German PCL centres in this multicentric, cross-sectional study from 2021 to 2022. The patients completed the dermatologic HRQoL questionnaire Skindex-29 and an investigator-designed 'CBCL-Questionnaire' with additional questions on HRQoL and clinical characteristics. RESULTS: The Skindex-29 revealed that HRQoL in CBCL patients is impaired on a mild to moderate level. The multiple regression analysis identified parameters like worries about dying, feeling prejudiced/discriminated and impairment of daily activities to be independently associated with impairment of HRQoL. Highest scores for HRQoL impairment were found in patients with primary cutaneous follicle centre lymphoma while on rituximab treatment and in patients with primary cutaneous marginal zone lymphoma while on watchful waiting. CONCLUSIONS: HRQoL is impaired in CBCL patients, even though, in the face of indolent disease course and favourable prognosis in the majority of cases. Of note, our investigator-designed tool identified worries about dying, feeling prejudiced/discriminated, and the type of treatment to have a negative impact on patients' HRQoL. Our study highlights the importance of a thorough patient-doctor communication to capture overall disease burden because generic HRQoL tools might lack of disease-specific items.

Convolutional LSTM-LSTM model for predicting the daily number of influenza patients in South Korea using satellite images.

OBJECTIVES: Influenza affects a considerable proportion of the global population each year, and meteorological conditions may have a significant impact on its transmission. In this study, we aimed to develop a prediction model for the number of influenza patients at the national level using satellite images and provide a basis for predicting influenza through satellite image data. STUDY DESIGN: We developed an influenza incidence prediction model using satellite images and influenza patient data. METHODS: We collected satellite images and daily influenza patient data from July 2014 to June 2019 and developed a convolutional long short-term memory (LSTM)-LSTM neural network model. The model with the lowest average of mean absolute error (MAE) was selected. RESULTS: The final model showed a high correlation between the predicted and actual number of influenza patients, with an average MAE of 5.9010 per million population. The model performed best with a 2-week time sequence. CONCLUSIONS: We developed a national-level prediction model using satellite images to predict influenza incidence. The model offers the advantage of nationwide analysis. These results may reduce the burden of influenza by enabling timely public health interventions.

Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms].

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

Measurement of the Λ_{c}

An absolute measurement of the Λ_{c}^{+} lifetime is reported using Λ_{c}^{+}→pK^{-}π^{+} decays in events reconstructed from data collected by the Belle II experiment at the SuperKEKB asymmetric-energy electron-positron collider. The total integrated luminosity of the data sample, which was collected at center-of-mass energies at or near the ϒ(4S) resonance, is 207.2 fb^{-1}. The result, τ(Λ_{c}^{+})=203.20±0.89±0.77 fs, where the first uncertainty is statistical and the second systematic, is the most precise measurement to date and is consistent with previous determinations.

Evidence of a New Excited Charmed Baryon Decaying to Σ_{c}(2455)

We present the study of B[over ¯]^{0}→Σ_{c}(2455)^{0,++}π^{±}p[over ¯] decays based on 772×10^{6} BB[over ¯] events collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The Σ_{c}(2455)^{0,++} candidates are reconstructed via their decay to Λ_{c}^{+}π^{∓} and Λ_{c}^{+} decays to pK^{-}π^{+}, pK_{S}^{0}, and Λπ^{+} final states. The corresponding branching fractions are measured to be B(B[over ¯]^{0}→Σ_{c}(2455)^{0}π^{+}p[over ¯])=(1.09±0.06±0.07)×10^{-4} and B(B[over ¯]^{0}→Σ_{c}(2455)^{++}π^{-}p[over ¯])=(1.84±0.11±0.12)×10^{-4}, which are consistent with the world average values with improved precision. A new structure is found in the M_{Σ_{c}(2455)^{0,++}π^{±}} spectrum with a significance of 4.2σ including systematic uncertainty. The structure is possibly an excited Λ_{c}^{+} and is tentatively named Λ_{c}(2910)^{+}. Its mass and width are measured to be (2913.8±5.6±3.8) MeV/c^{2} and (51.8±20.0±18.8) MeV, respectively. The products of branching fractions for the Λ_{c}(2910)^{+} are measured to be B(B[over ¯]^{0}→Λ_{c}(2910)^{+}p[over ¯])×B(Λ_{c}(2910)^{+}→Σ_{c}(2455)^{0}π^{+})=(9.5±3.6±1.6)×10^{-6} and B(B[over ¯]^{0}→Λ_{c}(2910)^{+}p[over ¯])×B(Λ_{c}(2910)^{+}→Σ_{c}(2455)^{++}π^{-})=(1.24±0.35±0.10)×10^{-5}. Here, the first and second uncertainties are statistical and systematic, respectively.

Search for the Lepton Flavor Violating Decays B

We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,µ), using the full data sample of 772×10^{6} BB[over ¯] pairs recorded by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.

First Measurement of the Michel Parameter ξ

We report the first measurement of the Michel parameter ξ^{'} in the τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decay with a new method proposed just recently. The measurement is based on the reconstruction of the τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} events with subsequent muon decay in flight in the Belle central drift chamber. The analyzed data sample of 988 fb^{-1} collected by the Belle detector corresponds to approximately 912×10^{6} τ^{+}τ^{-} pairs. We measure ξ^{'}=0.22±0.94(stat)±0.42(syst), which is in agreement with the standard model prediction of ξ^{'}=1. Statistical uncertainty dominates in this study, being a limiting factor, while systematic uncertainty is well under control. Our analysis proved the practicability of this promising method and its prospects for further precise measurement in future experiments.

Test of Light-Lepton Universality in the Rates of Inclusive Semileptonic B-Meson Decays at Belle II.

We present the first measurement of the ratio of branching fractions of inclusive semileptonic B-meson decays, R(X_{e/µ})=B(B→Xeν)/B(B→Xµν), a precision test of electron-muon universality, using data corresponding to 189 fb^{-1} from electron-positron collisions collected with the Belle II detector. In events where the partner B meson is fully reconstructed, we use fits to the lepton momentum spectra above 1.3 GeV/c to obtain R(X_{e/µ})=1.007±0.009(stat)±0.019(syst), which is the most precise lepton-universality test of its kind and agrees with the standard-model expectation.

First Observation of Λπ

Using the data sample of 980 fb^{-1} collected with the Belle detector operating at the KEKB asymmetric-energy e^{+}e^{-} collider, we present the results of an investigation of the Λπ^{+} and Λπ^{-} invariant mass distributions looking for substructure in the decay Λ_{c}^{+}→Λπ^{+}π^{+}π^{-}. We find a significant signal in each mass distribution. When interpreted as resonances, we find for the Λπ^{+} (Λπ^{-}) combination a mass of 1434.3±0.6(stat)±0.9(syst) MeV/c^{2} [1438.5±0.9(stat)±2.5(syst) MeV/c^{2}], an intrinsic width of 11.5±2.8(stat)±5.3(syst) MeV/c^{2} [33.0±7.5(stat)±23.6(syst) MeV/c^{2}] with a significance of 7.5σ (6.2σ). As these two signals are very close to the K[over ¯]N threshold, we also investigate the possibility of a K[over ¯]N cusp, and find that we cannot discriminate between these two interpretations due to the limited size of the data sample.

Search for Lepton-Flavor-Violating τ Decays to a Lepton and an Invisible Boson at Belle II.

We search for lepton-flavor-violating τ^{-}→e^{-}α and τ^{-}→µ^{-}α decays, where α is an invisible spin-0 boson. The search uses electron-positron collisions at 10.58 GeV center-of-mass energy with an integrated luminosity of 62.8 fb^{-1}, produced by the SuperKEKB collider and collected with the Belle II detector. We search for an excess in the lepton-energy spectrum of the known τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ} and τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decays. We report 95% confidence-level upper limits on the branching-fraction ratio B(τ^{-}→e^{-}α)/B(τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ}) in the range (1.1-9.7)×10^{-3} and on B(τ^{-}→µ^{-}α)/B(τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ}) in the range (0.7-12.2)×10^{-3} for α masses between 0 and 1.6 GeV/c^{2}. These results provide the most stringent bounds on invisible boson production from τ decays.

First Measurement of the B

We study B^{+}→π^{+}π^{0}π^{0} using 711 fb^{-1} of data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure an inclusive branching fraction of (19.0±1.5±1.4)×10^{-6} and an inclusive CP asymmetry of (9.2±6.8±0.7)%, where the first uncertainties are statistical and the second are systematic, and a B^{+}→ρ(770)^{+}π^{0} branching fraction of (11.2±1.1±0.9_{-1.6}^{+0.8})×10^{-6}, where the third uncertainty is due to possible interference with B^{+}→ρ(1450)^{+}π^{0}. We present the first observation of a structure around 1 GeV/c^{2} in the π^{0}π^{0} mass spectrum, with a significance of 6.4σ, and measure a branching fraction to be (6.9±0.9±0.6)×10^{-6}. We also report a measurement of local CP asymmetry in this structure.

Observation of e

We study the processes e^{+}e^{-}→ωχ_{bJ}(1P) (J=0, 1, or 2) using samples at center-of-mass energies sqrt[s]=10.701, 10.745, and 10.805 GeV, corresponding to 1.6, 9.8, and 4.7 fb^{-1} of integrated luminosity, respectively. These data were collected with the Belle II detector during special operations of the SuperKEKB collider above the ϒ(4S) resonance. We report the first observation of ωχ_{bJ}(1P) signals at sqrt[s]=10.745 GeV. By combining Belle II data with Belle results at sqrt[s]=10.867 GeV, we find energy dependencies of the Born cross sections for e^{+}e^{-}→ωχ_{b1,b2}(1P) to be consistent with the shape of the ϒ(10753) state. These data indicate that the internal structures of the ϒ(10753) and ϒ(10860) states may differ. Including data at sqrt[s]=10.653 GeV, we also search for the bottomonium equivalent of the X(3872) state decaying into ωϒ(1S). No significant signal is observed for masses between 10.45 and 10.65 GeV/c^{2}.

First Simultaneous Determination of Inclusive and Exclusive |V_{ub}|.

The first simultaneous determination of the absolute value of the Cabibbo-Kobayashi-Maskawa matrix element V_{ub} using inclusive and exclusive decays is performed with the full Belle data set at the ϒ(4S) resonance, corresponding to an integrated luminosity of 711 fb^{-1}. We analyze collision events in which one B meson is fully reconstructed in hadronic modes. This allows for the reconstruction of the hadronic X_{u} system of the semileptonic b→uℓν[over ¯]_{ℓ} decay. We separate exclusive B→πℓν[over ¯]_{ℓ} decays from other inclusive B→X_{u}ℓν[over ¯]_{ℓ} and backgrounds with a two-dimensional fit that utilizes the number of charged pions in the X_{u} system and the four-momentum transfer q^{2} between the B and X_{u} systems. Combining our measurement with information from lattice QCD and QCD calculations of the inclusive partial rate as well as external experimental information on the shape of the B→πℓν[over ¯]_{ℓ} form factor, we determine |V_{ub}^{excl}|=(3.78±0.23±0.16±0.14)×10^{-3} and |V_{ub}^{incl}|=(3.88±0.20±0.31±0.09)×10^{-3}, respectively, with the uncertainties being the statistical error, systematic errors, and theory errors. The ratio of |V_{ub}^{excl}|/|V_{ub}^{incl}|=0.97±0.12 is compatible with unity.

Search for a Heavy Neutrino in τ Decays at Belle.

We report on a search for a heavy Majorana neutrino in the decays τ^{-}→π^{-}ν_{h}, ν_{h}→π^{±}ℓ^{∓}, ℓ=e, µ. The results are obtained using the full data sample of 988 fb^{-1} collected with the Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider, which contains 912×10^{6} ττ pairs. We observe no significant signal and set 95% CL upper limits on the couplings of the heavy right-handed neutrinos to the conventional standard model left-handed neutrinos in the mass range 0.2-1.6 GeV/c^{2}. This is the first study of a mixed couplings of heavy neutrinos to τ leptons and light-flavor leptons.

Precise Measurement of the D_{s}

We measure the lifetime of the D_{s}^{+} meson using a data sample of 207 fb^{-1} collected by the Belle II experiment running at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The lifetime is determined by fitting the decay-time distribution of a sample of 116×10^{3} D_{s}^{+}→ϕπ^{+} decays. Our result is τ_{D_{s}^{+}}=(499.5±1.7±0.9) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.

Search for an Invisible Z

The L_{µ}-L_{τ} extension of the standard model predicts the existence of a lepton-flavor-universality-violating Z^{'} boson that couples only to the heavier lepton families. We search for such a Z^{'} through its invisible decay in the process e^{+}e^{-}→µ^{+}µ^{-}Z^{'}. We use a sample of electron-positron collisions at a center-of-mass energy of 10.58 GeV collected by the Belle II experiment in 2019-2020, corresponding to an integrated luminosity of 79.7 fb^{-1}. We find no excess over the expected standard-model background. We set 90%-confidence-level upper limits on the cross section for this process as well as on the coupling of the model, which ranges from 3×10^{-3} at low Z^{'} masses to 1 at Z^{'} masses of 8 GeV/c^{2}.

How does attribute ambiguity improve memory?

The memory effects of semantic attributes (e.g., concreteness, familiarity, valence) have long been studied by manipulating their average perceived intensities, as quantified in word rating norms. The semantic ambiguity hypothesis specifies that the uncertainty as well as the intensity of semantic attributes is processed when words are encoded. Testing that hypothesis requires a normed measure of ambiguity, so that ambiguity and intensity can be manipulated independently. The standard deviation (SD) of intensity ratings has been used for that purpose, which has produced three characteristic ambiguity effects. Owing to the recency of such research, fundamental questions remain about the validity of this method of measuring ambiguity and about its process-level effects on memory. In a validity experiment, we found that the rating SDs of six semantic attributes (arousal, concreteness, familiarity, meaningfulness, negative valence, positive valence) passed tests of concurrent and predictive validity. In three memory experiments, we found that manipulating rating SDs had a specific effect on retrieval: It influenced subjects' ability to use reconstructive retrieval to recall words. That pattern was predicted by the current theoretical explanation of how ambiguity benefits memory.

Memory effects of semantic attributes: A method of controlling attribute contamination.

Rating norms for semantic attributes (e.g., concreteness, familiarity, valence) are widely used to study the content that people process as they encode meaningful material. Intensity ratings of individual attributes have been manipulated in numerous experiments with a range of memory paradigms, but those manipulations are contaminated by substantial correlations with the intensity ratings of other attributes. A method of controlling such contamination is needed, which requires a determination of how many distinct attributes there are among the large collection of attributes for which published norms are available. Identification of overlapping words in multiple rating projects yielded a data base containing normed values for each word's perceived intensity (M rating) and ambiguity (rating SD) on 20 different attributes. Principal component analyses then revealed that the intensity space was spanned by just three latent semantic attributes, and the ambiguity space was spanned by five. Psychologically, the big three intensity factors (emotional valence, size, age) were highly interpretable, as were the big five ambiguity factors (discrete emotion, emotional valence, age, meaningfulness, and verbatim memory). We provide a data base of intensity and ambiguity factor scores that can be used to conduct uncontaminated studies of the memory effects of the intensity and ambiguity of latent semantic attributes.